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  • 1.
    Blais, David R.
    et al.
    Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.
    Vascotto, Sandy G.
    Eye Institute, University of Ottawa, Ottawa, Ontario, Canada..
    Griffith, May
    Eye Institute, and the Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada.
    Altosaar, Illimar
    Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.
    LBP and CD14 secreted in tears by the lacrimal glands modulate the LPS response of corneal epithelial cells2005In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 46, no 11, p. 4235-4244Article in journal (Refereed)
    Abstract [en]

    PURPOSE. Lipopolysaccharide (LPS) is one of the most powerful bacterial virulence factors in terms of proinflammatory properties and is likely to contribute to corneal bacterial keratitis. Better understanding of the spatial expression of the LPS receptor components at the tear - corneal interface might facilitate enhanced functions of the LPS receptor complex in ocular defense against Gram-negative infections. METHODS. The expression of LPS-binding protein (LBP), CD14, toll-like receptor (TLR)-4, and MD-2 in human lacrimal glands, reflex tears, and corneal epithelia was examined by ELISA, RT-PCR, Western blot analysis, and immunofluorescence. The release of proinflammatory cytokines after the activation of primary and immortalized corneal epithelial cells with LPS and human tears was measured by ELISA. RESULTS. LBP and CD14 proteins were detected in reflex human tears. Human lacrimal glands and corneal epithelia expressed LBP, CD14, TLR4, and MD-2 mRNAs and proteins. In the corneal epithelium, LBP was mainly expressed by superficial and basal epithelial cells, whereas CD14, TLR4, and MD-2 expression were limited to the wing and basal epithelial cells. In a dose-dependant manner, tear CD14 and LBP mediated the secretion of interleukin (IL)-6 and IL-8 by corneal epithelia cells when challenged with LPS. CONCLUSIONS. Tear CD14 and LBP complemented the LPS receptor complex expressed by the corneal epithelia to trigger an immune response in the presence of LPS. The complementation of these tear and corneal immune proteins could play an important role in LPS recognition and signaling and, therefore, could modulate ocular innate immunity.

  • 2.
    Bourghardt Peebo, Beatrice
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    Fagerholm, Per
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    Traneus-Rockert, Catharina
    Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Clinical Genetics.
    Lagali, Neil
    Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH. Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Linköping University, Faculty of Health Sciences.
    Cellular-Level Characterization of Lymph Vessels in Live, Unlabeled Corneas by In Vivo Confocal Microscopy2010In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 51, no 2, p. 830-835Article in journal (Refereed)
    Abstract [en]

    PURPOSE. To determine whether in vivo confocal microscopy (IVCM) of the cornea can be used for the label-free detection and monitoring of lymph vessels in live corneas.

    METHODS. Parallel corneal hemangiogenesis and lymphangiogenesis was induced by the placement of a single suture in one cornea of male Wistar rats. Fourteen days after suture placement and under general anesthesia, laser-scanning IVCM was performed in the vascularized region. Corneas were subsequently excised for flat-mount double immunofluorescence with a pan-endothelial marker (PECAM-1/CD31) and a lymphatic endothelial specific marker (LYVE-1). Using the suture area and prominent blood vessels as points of reference, the identical microscopic region was located in both fluorescent and archived in vivo images. Additionally, vessel diameter, lumen contrast, and cell diameter and velocity within vessels were quantified from in vivo images.

    RESULTS. Comparison of identical corneal regions in fluorescence and in vivo revealed prominent CD31(+)/LYVE-1(3+) lymph vessels that were visible in vivo. In vivo, corneal lymph vessels were located in the vascularized area in the same focal plane as blood vessels but had a darker lumen (P andlt; 0.001) sparsely populated by highly reflective cells with diameters similar to those of leukocytes in blood vessels (P = 0.61). Cell velocity in lymph vessels was significantly reduced compared with blood particle velocity (P andlt; 0.001). Morphologic characteristics enabled subsequent identification of corneal lymphatics in live, vascularized rat corneas before immunofluorescence labeling.

    CONCLUSIONS. IVCM enabled the nondestructive, label-free, in vivo detection of corneal lymphatics. IVCM provides the possibility of observing lymphatic activity in the same live corneas longitudinally and, as a clinical instrument, of monitoring corneal lymphatics in live human subjects.

  • 3.
    Bourghardt Peebo, Beatrice
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Ophthalmology UHL/MH.
    Fagerholm, Per
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Ophthalmology UHL/MH.
    Traneus-Rockert, Catharina
    Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Lagali, Neil
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Ophthalmology UHL/MH.
    Time-Lapse In Vivo Imaging of Corneal Angiogenesis: The Role of Inflammatory Cells in Capillary Sprouting2011In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 52, no 6, p. 3060-3068Article in journal (Refereed)
    Abstract [en]

    PURPOSE. To elucidate the temporal sequence of events leading to new capillary sprouting in inflammatory corneal angiogenesis.

    METHODS. Angiogenesis was induced by corneal suture placement in Wistar rats. The inflamed region was examined by time-lapse in vivo confocal microscopy for up to 7 days. At 6 and 12 hours and 1, 2, 4, and 7 days, corneas were excised for flat mount immunofluorescence with primary antibodies for CD31, CD34, CD45, CD11b, CD11c, Ki-M2R, NG2, and alpha-SMA. From days 0 to 4, the in vivo extravasation and expansion characteristics of single limbal vessels were quantified.

    RESULTS. Starting hours after induction and peaking at day 1, CD45(+)CD11b(+) myeloid cells extravasated from limbal vessels and formed endothelium-free tunnels within the stroma en route to the inflammatory stimulus. Limbal vessel diameter tripled on days 2 to 3 as vascular buds emerged and transformed into perfused capillary sprouts less than 1 day later. A subset of spindle-shaped CD11b(+) myeloid-lineage cells, but not dendritic cells or mature macrophages, appeared to directly facilitate further capillary sprout growth. These cells incorporated into vascular endothelium near the sprout tip, co-expressing endothelial marker CD31. Sprouts had perfusion characteristics distinct from feeder vessels and many sprout tips were open-ended.

    CONCLUSIONS. Time-lapse in vivo corneal confocal microscopy can be used to track a temporal sequence of events in corneal angiogenesis. The technique has revealed potential roles for myeloid cells in promoting vessel sprouting in an inflammatory corneal setting.

  • 4.
    Crafoord, Sven
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology .
    Algvere, Peep
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology . Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    Seregard, S
    Orebro Med Ctr Hosp, Dept Ophthalmol, S-70185 Orebro, Sweden St Eriks Eye Hosp, Karolinska Inst, Stockholm, Sweden Linkoping Univ, Dept Ophthalmol, Linkoping, Sweden.
    Dafgard-Kopp, E
    Orebro Med Ctr Hosp, Dept Ophthalmol, S-70185 Orebro, Sweden St Eriks Eye Hosp, Karolinska Inst, Stockholm, Sweden Linkoping Univ, Dept Ophthalmol, Linkoping, Sweden.
    Cellular migration into neural retina following implantation of melanin granules to the subretinal space.2000In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 41, no 4, p. 4545B492-Conference paper (Other academic)
  • 5.
    Fagerholm, Per
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology . Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    Gan, Lisha
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology .
    Palmblad, J
    Expression of VEGF and its receptor VEGFR-2/flk-1 following rabbit corneal alkali burn in the presence and absence of granulocytes2002In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 43, p. 4210-Conference paper (Other academic)
  • 6.
    Frennesson, Christina
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology . Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    Larsson, R
    Hultman, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology . Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Clinical Genetics.
    Nilsson, SG
    Drusen and choroidal neovascularization (CNV) in patients with dense deposit disease (membrano-proliferative glomerulonephritis type II). Favourable effect of photodynamic treatment (PDT)2003In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 44, p. 1774-Conference paper (Other academic)
  • 7.
    Frennesson, Christina
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology . Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    Nilsson, Sven Erik
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology .
    Encouraging results with photodynamic treatment (PDT) in a clinical patient material of age-related macular degeneration (AMD) and other diagnoses: Leakage stopped with fewer treatments than in the Tap and Vip studies2002In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 43, p. 593-Conference paper (Other academic)
  • 8.
    Frennesson, Christina
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology . Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    Weingeist, D
    Linkoping Univ, Dept Ophthalmol, Linkoping, Sweden Univ Iowa, Ctr Macular Degenerat, Dept Ophthalmol & Visual Sci, Iowa City, IA USA.
    Nienhaus, H
    Linkoping Univ, Dept Ophthalmol, Linkoping, Sweden Univ Iowa, Ctr Macular Degenerat, Dept Ophthalmol & Visual Sci, Iowa City, IA USA.
    Mullins, RF
    Linkoping Univ, Dept Ophthalmol, Linkoping, Sweden Univ Iowa, Ctr Macular Degenerat, Dept Ophthalmol & Visual Sci, Iowa City, IA USA.
    Hageman, GS
    Linkoping Univ, Dept Ophthalmol, Linkoping, Sweden Univ Iowa, Ctr Macular Degenerat, Dept Ophthalmol & Visual Sci, Iowa City, IA USA.
    Vitronectin distribution in the choroidal stroma and Bruch's membrane as related to age and age-related macular degeneration.2000In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 41, no 4, p. 120B120-Conference paper (Other academic)
  • 9.
    Gan, Lisha
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology .
    Fagerholm, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology . Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    Blalock, TD
    Schultz, GS
    Connective tissue growth factor (CTGF) in the alkali wounded corneas2002In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 43, p. 4207-Conference paper (Other academic)
  • 10.
    Gan, Lisha
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology .
    Hakim, M
    Mintsioulis, G
    Griffith, M
    Human corneal cellular response to the synthetic stromal matrix replacements2003In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 44, p. 4693-Conference paper (Other academic)
  • 11.
    Germundsson, Johan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Fagerholm, Per
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Ophthalmology UHL/MH.
    Koulikovska, Marina
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Ophthalmology UHL/MH.
    Lagali, Neil
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Ophthalmology UHL/MH.
    An Accurate Method to Determine Bowmans Layer Thickness In Vivo in the Human Cornea2012In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 53, no 4, p. 2354-2359Article in journal (Refereed)
    Abstract [en]

    PURPOSE. To determine an accurate value for Bowmans layer (BL) thickness in vivo in humans. less thanbrgreater than less thanbrgreater thanMETHODS. Seventeen corneal transplant patients were examined preoperatively by laser-scanning in vivo confocal microscopy (IVCM), and corneal buttons were removed post-operatively and sectioned for light microscopy (LM). Nine corneas with uniformly thick BL by LM were used for thickness measurement. In the uniformly thick samples, probable overestimation of BL thickness in vivo by a first in vivo method (Method 1) led to the development of a revised in vivo method (Method 2). Method 2 was used to measure BL thickness in 20 healthy volunteers. less thanbrgreater than less thanbrgreater thanRESULTS. In nine patients, mean BL thickness prior to transplantation was 13.7 +/- 1.6 mu m by IVCM (Method 1) while BL thickness of the removed corneal button was 9.7 +/- 1.7 mu m by LM (P andlt; 0.001). The correlation of BL thickness between IVCM (Method 1) and LM was poor (P = 0.226). In 20 right eyes of 20 normal corneas, both in vivo methods were used to determine BL thickness. Mean BL thickness by Method 1 was 13.2 +/- 1.6 mu m and by Method 2 was 9.1 +/- 1.4 mu m (P andlt; 0.001). BL thickness measurements by both in vivo methods were highly correlated (P andlt; 0.001). less thanbrgreater than less thanbrgreater thanCONCLUSION. BL thickness by a revised in vivo method was close to LM values in this study and to values reported in fixed tissue in other studies. The authors believe this revised method provides the most accurate estimates of BL thickness in vivo to date.

  • 12.
    Germundsson, Johan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Karanis, Georgios
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Fagerholm, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    Lagali, Neil
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    Age-Related Thinning of Bowman's Layer in the Human Cornea In Vivo2013In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 54, no 9, p. 6143-6149Article in journal (Refereed)
    Abstract [en]

    Purpose. To determine the thickness of Bowman's layer (BL) in vivo in a healthy population and to determine its variation with age.

    Methods. Eighty-two subjects aged 15 to 88 years with clear, healthy corneas were examined bilaterally with laser scanning in vivo confocal microscopy (IVCM). Bowman's layer thickness was determined from IVCM images of anterior and posterior BL boundaries. For a given eye, BL thickness was averaged across four central locations by two independent observers. In addition, central corneal thickness was measured by time-domain optical coherence tomography.

    Results. A significant negative correlation of BL thickness with age was found in right eyes (Pearson r = −0.579, P < 0.0001) and in left eyes (r = −0.558, P < 0.0001). Linear regression analysis yielded a decline in BL thickness of 0.06 μm per year. In 41 older subjects (mean age, 64.4 years), BL thickness was significantly thinner (mean ± SD, 8.6 ± 1.7 μm in right eyes) than that in 41 younger subjects (mean age, 31.6 years) (mean ± SD, 10.7 ± 1.6 μm in right eyes) (P < 0.001). No correlation of corneal thickness with age or of BL thickness with corneal thickness was observed. Strong intereye correlations in BL thickness (r = 0.771, P < 0.0001) and corneal thickness (r = 0.969, P < 0.001) were found.

    Conclusions. Bowman's layer thins with age in the normal cornea, losing one-third of its thickness between the ages of 20 and 80 years. In vivo measurement of BL thickness by IVCM could aid in clinical assessment and planned treatments of the anterior cornea.

  • 13.
    Germundsson, Johan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences.
    Lagali, Neil
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    Pathologically reduced subbasal nerve density in epithelial basement membrane dystrophy is unaltered by phototherapeutic keratectomy treatment2014In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 55, no 3, p. 1835-1841Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To investigate the effect of phototherapeutic keratectomy (PTK) treatment on corneal epithelial wing cell and corneal subbasal nerve density in epithelial basement membrane dystrophy (EBMD).

    METHODS: A total of 39 patients with EBMD who underwent PTK treatment, 40 healthy volunteers, and 24 untreated eyes with EBMD were examined with laser-scanning in vivo confocal microscopy (IVCM). Corneal subbasal nerves and epithelial wing cells were manually quantified from IVCM images by two observers, while epithelial wing cells were additionally quantified by a fully automated method.

    RESULTS: Subbasal nerve density was significantly reduced in untreated (10,164 ± 4139 μm/mm(2); n = 24) and PTK-treated (10,624 ± 4479 μm/mm(2); n = 39) EBMD eyes, relative to healthy controls (18,241 ± 4479 μm/mm(2); n = 40) (P < 0.001). Subbasal nerve density in PTK-treated and untreated eyes did not differ (P > 0.05). Epithelial wing cell density did not differ between PTK-treated and untreated EBMD eyes, by either manual or automated analysis; however, epithelial wing cell density in PTK-treated EBMD corneas was significantly reduced (P = 0.008) relative to healthy corneas, by automated cell counting.

    CONCLUSIONS: Subbasal nerve density in EBMD is reduced by 45% and recovers only to the reduced level in the long term after PTK treatment, whereas epithelial wing cell density in EBMD is not affected by PTK in the long term. Fully automated cell analysis from IVCM images could provide an objective, standardized means to quantify and compare corneal cell densities in future studies.

  • 14.
    Hackett, Joanne M.
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology.
    Lagali, Neil
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    Merrett, Kimberley
    University of Ottawa Eye Institute.
    Edelhauser, Henry
    Emory University School of Medicine.
    Sun, Yifei
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Gan, Lisha
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Linköping University, Faculty of Health Sciences.
    Griffith, May
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Linköping University, Faculty of Health Sciences.
    Fagerholm, Per
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    Biosynthetic corneal implants for replacement of pathologic corneal tissue: performance in a controlled rabbit alkali burn model2011In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 52, no 2, p. 651-657Article in journal (Refereed)
    Abstract [en]

    Purpose: To evaluate the performance of structurally reinforced, stabilized recombinant human collagen-phosphorylcholine (RHCIII-MPC) hydrogels as corneal substitutes in a rabbit model of severe corneal damage.

    Methods: One eye each of 12 rabbits received a deep corneal alkali wound. Four corneas were implanted with RHCIII-MPC hydrogels. The other eight control corneas were implanted with either allografts or a simple crosslinked RHCIII hydrogel. In all cases, 6.25 mm diameter, 350 µm thick buttons were implanted by anterior lamellar keratoplasty to replace damaged corneal tissue. Implants were followed for nine months by clinical examination and in vivo confocal microscopy, after which implanted corneas were removed and processed for histopathological and ultrastructural examination.

    Results: Alkali exposure induced extensive central corneal scarring, ocular surface irregularity, and neovascularization in one case. All implants showed complete epithelial coverage by four weeks post-operative, but with accompanying suture-induced vascularization in 6/12 cases. A stable, stratified epithelium with hemidesmosomal adhesion complexes regenerated over all implants, and subbasal nerve regeneration was observed in allograft and RHCIII-MPC implants. Initially acellular biosynthetic implants were populated with host-derived keratocytes as stromal haze subsided and stromal collagen was remodeled. Notably, RHCIII-MPC implants exhibited resistance to vascular ingrowth while supporting endogenous cell and nerve repopulation.

    Conclusion: Biosynthetic implants based on RHC promoted cell and nerve repopulation in alkali burned rabbit eyes. In RHCIII-MPC implants, evidence of an enhanced resistance to neovascularization was additionally noted.

  • 15.
    He, Min
    et al.
    Harvard Medical Sch, MA USA; Shanxi Medical University, Peoples R China.
    Storr-Paulsen, Thomas
    Harvard Medical Sch, MA USA; Aarhus University Hospital NBG, Denmark.
    Wang, Annie L.
    Harvard Medical Sch, MA USA.
    Ghezzi, Chiara E.
    Tufts University, MA 02155 USA.
    Wang, Siran
    Tufts University, MA 02155 USA.
    Fullana, Matthew
    Case Western Reserve University, OH 44106 USA.
    Karamichos, Dimitrios
    University of Oklahoma, OK USA.
    Utheim, Tor P.
    Harvard Medical Sch, MA USA; University of Oslo, Norway; Vestre Viken Hospital Trust, Norway; University of Coll Southeast Norway, Norway.
    Islam, Rakibul
    Harvard Medical Sch, MA USA; University of Oslo, Norway.
    Griffith, May
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Institute, Sweden.
    Islam, Mohammad Mirazul Mirazul
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Institute, Sweden.
    Hodges, Robin R.
    Harvard Medical Sch, MA USA.
    Wnek, Gary E.
    Case Western Reserve University, OH 44106 USA.
    Kaplan, David L.
    Tufts University, MA 02155 USA.
    Dartt, Darlene A.
    Harvard Medical Sch, MA USA.
    Artificial Polymeric Scaffolds as Extracellular Matrix Substitutes for Autologous Conjunctival Goblet Cell Expansion2016In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 57, no 14, p. 6134-6146Article in journal (Refereed)
    Abstract [en]

    PURPOSE. We fabricated and investigated polymeric scaffolds that can substitute for the conjunctival extracellular matrix to provide a substrate for autologous expansion of human conjunctival goblet cells in culture. METHODS. We fabricated two hydrogels and two silk films: (1) recombinant human collagen (RHC) hydrogel, (2) recombinant human collagen 2-methacryloylxyethyl phosphorylcholine (RHC-MPC) hydrogel, (3) arginine-glycine-aspartic acid (RGD) modified silk, and (4) poly-D-lysine (PDL) coated silk, and four electrospun scaffolds: (1) collagen, (2) poly(acrylic acid) (PAA), (3) poly(caprolactone) (PCL), and (4) poly(vinyl alcohol) (PVA). Coverslips and polyethylene terephthalate (PET) were used for comparison. Human conjunctival explants were cultured on scaffolds for 9 to 15 days. Cell viability, outgrowth area, and the percentage of cells expressing markers for stratified squamous epithelial cells (cytokeratin 4) and goblet cells (cytokeratin 7) were determined. RESULTS. Most of cells grown on all scaffolds were viable except for PCL in which only 3.6 +/- 2.2% of the cells were viable. No cells attached to PVA scaffold. The outgrowth was greatest on PDL-silk and PET. Outgrowth was smallest on PCL. All cells were CK7-positive on RHCMPC while 84.7 +/- 6.9% of cells expressed CK7 on PDL-silk. For PCL, 87.10 +/- 3.17% of cells were CK7-positive compared to PET where 67.10 +/- 12.08% of cells were CK7-positive cells. CONCLUSIONS. Biopolymer substrates in the form of hydrogels and silk films provided for better adherence, proliferation, and differentiation than the electrospun scaffolds and could be used for conjunctival goblet cell expansion for eventual transplantation once undifferentiated and stratified squamous cells are included. Useful polymer scaffold design characteristics have emerged from this study.

  • 16.
    Koulikovska, Marina
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology . Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    Podskochy, Alexander
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology . Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    Fagerholm, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology . Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    Expression of the chaperonin containing T-complex polypeptide 1 chaperonin subunit during corneal wound healing2003In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 44, p. 854-Conference paper (Other academic)
  • 17.
    Lagali, Neil
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    Edén, Ulla
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences.
    Paaske Utheim, Tor
    Oslo University Hospital, Norway.
    Chen, Xiangjun
    Synslaser Kirurgi AS, Norway.
    Riise, Ruth
    Innland Hospital, Norway.
    Delby, Anette
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    Fagerholm, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    In Vivo Morphology of the Limbal Palisades of Vogt Correlates With Progressive Stem Cell Deficiency in Aniridia-Related Keratopathy2013In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 54, no 8, p. 5333-5342Article in journal (Refereed)
    Abstract [en]

    Purpose. To investigate morphologic alterations in the limbal palisades of Vogt in a progressive form of limbal stem cell deficiency.

    Methods. Twenty Norwegian subjects (40 eyes) with congenital aniridia and 9 healthy family members (18 eyes) without aniridia were examined. Clinical grade of aniridia-related keratopathy (ARK) was assessed by slit-lamp biomicroscopy, and tear production and quality, corneal thickness, and sensitivity were additionally measured. The superior and inferior limbal palisades of Vogt and central cornea were examined by laser scanning in vivo confocal microscopy (IVCM).

    Results. In an aniridia patient with grade 0 ARK, a transparent cornea and normal limbal palisade morphology were found. In grade 1 ARK, 5 of 12 eyes had degraded palisade structures. In the remaining grade 1 eyes and in all 20 eyes with stage 2, 3, and 4 ARK, palisade structures were absent by IVCM. Increasing ARK grade significantly correlated with reduced visual acuity and corneal sensitivity, increased corneal thickness, degree of degradation of superior and inferior palisade structures, reduced peripheral nerves, increased inflammatory cell invasion, and reduced density of basal epithelial cells and central subbasal nerves. Moreover, limbal basal epithelial cell density and central corneal subbasal nerve density were both significantly reduced in aniridia compared to healthy corneas (P = 0.002 and 0.003, respectively).

    Conclusions. Progression of limbal stem cell deficiency in aniridia correlates with degradation of palisade structures, gradual transformation of epithelial phenotype, onset of inflammation, and a corneal nerve deficit. IVCM can be useful in monitoring early- to late-stage degenerative changes in stem cell–deficient patients.

  • 18.
    Lagali, Neil
    et al.
    University of Ottawa Eye Institute.
    Griffith, May
    Univ Ottawa, Dept Cellular & Mol Med, Ottawa, ON, Canada.
    Fagerholm, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    Merrett, Kimberley
    University of Ottawa Eye Institute.
    Huynh, Melissa
    University of Ottawa Eye Institute.
    Munger, Rejean
    University of Ottawa Eye Institute.
    Innervation of tissue-engineered recombinant human collagen-based corneal substitutes: A comparative in vivo confocal microscopy study2008In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 49, no 9, p. 3895-3902Article in journal (Refereed)
    Abstract [en]

    PURPOSE. To compare reinnervation in recombinant human collagen-based corneal substitutes with allografts during a 1-year postimplantation follow-up period in pigs. A retrospective comparison to innervation in porcine collagen-based biosynthetic grafts was also performed. METHODS. Pigs received a corneal allograft or a substitute made of either recombinant human type-I or -III collagen. In vivo confocal microscopic examination of the central cornea of surgical and untouched control eyes before surgery and at 2, 6, and 12 months after surgery was performed to quantify the number, density, and diameter of nerves at various corneal depths. RESULTS. By 12 months after surgery, the number and density of regenerated nerves in the anterior and deep anterior corneal stroma recovered to preoperative and control levels in both types of substitute grafts and in the allografts. In the subepithelial and subbasal regions, however, significantly fewer nerves were detected relative to those in control subjects at 12 months, regardless of graft type ( P < 0.05), similar to the behavior of porcine collagen-based biosynthetic grafts. An absence of thick stromal nerve trunks (diameter, > 10 mu m) in all grafts, irrespective of material type, indicated that nerve regeneration in grafts was accompanied by persistent morphologic changes. CONCLUSIONS. Nerve regeneration in recombinant human collagen-based biosynthetic corneal grafts proceeded similarly to that in allograft tissue, demonstrating the suitability of recombinant human collagen constructs as nerve-friendly corneal substitutes. Furthermore, only minor differences were noted between type-I and -III collagen grafts, indicating an insensitivity of nerve regeneration to initial collagen type.

  • 19.
    Lagali, Neil
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    Poletti, Enea
    University of Padua, Italy.
    Patel, Dipika V.
    University of Auckland, New Zealand.
    McGhee, Charles N. J.
    University of Auckland, New Zealand.
    Hamrah, Pedram
    Harvard University, MA USA.
    Kheirkhah, Ahmad
    Harvard University, MA USA.
    Tavakoli, Mitra
    University of Manchester, England.
    Petropoulos, Ioannis N.
    University of Manchester, England; Qatar Fdn, Qatar.
    Malik, Rayaz A.
    University of Manchester, England; Qatar Fdn, Qatar.
    Paaske Utheim, Tor
    Oslo University Hospital, Norway; University of Oslo, Norway.
    Zhivov, Andrey
    University of Rostock, Germany.
    Stachs, Oliver
    University of Rostock, Germany.
    Falke, Karen
    University of Rostock, Germany.
    Peschel, Sabine
    University of Rostock, Germany.
    Guthoff, Rudolf
    University of Rostock, Germany.
    Chao, Cecilia
    University of New S Wales, Australia.
    Golebiowski, Blanka
    University of New S Wales, Australia.
    Stapleton, Fiona
    University of New S Wales, Australia.
    Ruggeri, Alfredo
    University of Padua, Italy.
    Focused Tortuosity Definitions Based on Expert Clinical Assessment of Corneal Subbasal Nerves2015In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 56, no 9, p. 5102-5109Article in journal (Refereed)
    Abstract [en]

    PURPOSE. We examined agreement among experts in the assessment of corneal subbasal nerve tortuosity. METHODS. Images of corneal subbasal nerves were obtained from investigators at seven sites (Auckland, Boston, Linkoping, Manchester, Oslo, Rostock, and Sydney) using laser-scanning in vivo confocal microscopy. A set of 30 images was assembled and ordered by increasing tortuosity by 10 expert graders from the seven sites. In a first experiment, graders assessed tortuosity without a specific definition and performed grading three times, with at least 1 week between sessions. In a second experiment, graders assessed the same image set using four focused tortuosity definitions. Intersession and intergrader repeatability for the experiments were determined using the Spearman rank correlation. RESULTS. Expert graders without a specific tortuosity definition had high intersession (Spearman correlation coefficient 0.80), but poor intergrader (0.62) repeatability. Specific definitions improved intergrader repeatability to 0.79. In particular, tortuosity defined by frequent small-amplitude directional changes (short range tortuosity) or by infrequent large-amplitude directional changes (long range tortuosity), indicated largely independent measures and resulted in improved repeatability across the graders. A further refinement, grading only the most tortuous nerve in a given image, improved the average correlation of a given graders ordering of images with the group average to 0.86 to 0.90. CONCLUSIONS. Definitions of tortuosity specifying short or long-range tortuosity and considering only the most tortuous nerve in an image improved the agreement in tortuosity grading among a group of expert observers. These definitions could improve accuracy and consistency in quantifying subbasal nerve tortuosity in clinical studies.

  • 20.
    Lagali, Neil S
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    Allgeier, Stephan
    Institute for Applied Computer Science, Karlsruhe Institute of Technology, Karlsruhe, Germany.
    Guimarães, Pedro
    Department of Information Engineering, University of Padova, Padova, Italy.
    Badian, Reza A.
    Faculty of Health Sciences, University College of Southeast Norway, Kongsberg, Norway; Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway; Department of Ophthalmology, Stavanger University Hospital, Stavanger/Clinical Institute 1, Faculty of Medicine, University of Bergen, Bergen, Norway.
    Ruggeri, Alfredo
    Department of Information Engineering, University of Padova, Padova, Italy.
    Köhler, Bernd
    Institute for Applied Computer Science, Karlsruhe Institute of Technology, Karlsruhe, Germany.
    Utheim, Tor Paaske
    Faculty of Health Sciences, University College of Southeast Norway, Kongsberg, Norway; Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway.
    Peebo, Beatrice
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    Peterson, Magnus
    Department of Public Health and Caring Sciences, Section of Family Medicine and Preventive Medicine, Uppsala University, Uppsala, Sweden.
    Dahlin, Lars B.
    Department of Translational Medicine-Hand Surgery, Lund University, Skåne University Hospital, Malmö, Sweden.
    Rolandsson, Olov
    Department of Public Health and Clinical Medicine, Section of Family Medicine, Umeå University, Umeå, Sweden.
    Reduced Corneal Nerve Fiber Density in Type 2 Diabetes by Wide-Area Mosaic Analysis2017In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 58, no 14, p. 6318-6327Article in journal (Refereed)
    Abstract [en]

    Purpose: To determine if corneal subbasal nerve plexus (SBP) parameters derived from wide-area depth-corrected mosaic images are associated with type 2 diabetes.

    Methods: One hundred sixty-three mosaics were produced from eyes of 82 subjects by laser-scanning in vivo confocal microscopy (IVCM). Subjects were of the same age, without (43 subjects) or with type 2 diabetes (39 subjects). Mosaic corneal nerve fiber length density (mCNFL) and apical whorl corneal nerve fiber length density (wCNFL) were quantified and related to the presence and duration of diabetes (short duration < 10 years and long duration ≥ 10 years).

    Results: In mosaics with a mean size of 6 mm2 in subjects aged 69.1 ± 1.2 years, mCNFL in type 2 diabetes was reduced relative to nondiabetic subjects (13.1 ± 4.2 vs. 15.0 ± 3.2 mm/mm2, P = 0.018). Also reduced relative to nondiabetic subjects was mCNFL in both short-duration (14.0 ± 4.0 mm/mm2, 3.2 ± 3.9 years since diagnosis) and long-duration diabetes (12.7 ± 4.2 mm/mm2, 15.4 ± 4.2 years since diagnosis; ANOVA P = 0.023). Lower mCNFL was associated with presence of diabetes (P = 0.032) and increased hemoglobin A1c (HbA1c) levels (P = 0.047). By contrast, wCNFL was unaffected by diabetes or HbA1c (P > 0.05). Global SBP patterns revealed marked degeneration of secondary nerve fiber branches outside the whorl region in long-duration diabetes.

    Conclusions: Wide-area mosaic images provide reference values for mCNFL and wCNFL and reveal a progressive degeneration of the SBP with increasing duration of type 2 diabetes.

  • 21.
    Lagali, Neil
    et al.
    Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    Stenevi, Ulf
    Sahlgrens University Hospital.
    Fagerholm, Per
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    Claesson, Margareta
    Sahlgrens University Hospital.
    Letter: Author Response: Donor Cell Survival in Corneal Grafts2010In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 51, no 8, p. 3843-3845Article in journal (Other academic)
    Abstract [en]

    n/a

  • 22.
    Lagali, N.S.
    et al.
    University of Ottawa Eye Institute, University of Ottawa, Ottawa, ON, Canada.
    Griffith, M.
    University of Ottawa Eye Institute, University of Ottawa, Ottawa, ON, Canada, Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada.
    Shinozaki, N.
    TDC Eye Bank and Cornea Centre, Ichikawa General Hospital, Chiba, Japan.
    Fagerholm, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    Munger, R.
    University of Ottawa Eye Institute, University of Ottawa, Ottawa, ON, Canada, University of Ottawa Eye Institute, Ottawa Hospital-General Campus, 501 Smyth Road, Ottawa, ON K1H 8L6, Canada.
    Innervation of tissue-engineered corneal implants in a porcine model: A 1-year in vivo confocal microscopy study2007In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 48, no 8, p. 3537-3544Article in journal (Refereed)
    Abstract [en]

    PURPOSE. To examine the pattern of nerve regeneration within tissue-engineered corneal substitutes grafted into host porcine corneas over a 1-year postoperative period. METHODS. Biodegradable corneal substitutes from cross-linked collagen were implanted into the left eyes of 12 pigs by deep lamellar keratoplasty. Regeneration of severed nerves into the central implant region was investigated with in vivo confocal microscopy. Both implant-recipient and control (right) eyes were examined before surgery and 2, 6, 10, and 12 months after surgery, to quantify the number, density, diameter, and branching of nerve fiber bundles at various corneal depths. Transmission electron microscopy was used to confirm the presence of nerve bundles. RESULTS. Two months after surgery, corneal nerve ingrowth was observed within the deep anterior stroma, with a number and density of regenerated nerves significantly higher than in nonsurgical control eyes (P < 0.01). Nerves within the superficial anterior stroma regenerated by 6 to 10 months after surgery, and the first subbasal epithelial nerves were seen 10 months after surgery. After 1 year, subbasal nerve density recovered to preoperative levels. Nerve fibers in the deep anterior stroma remained significantly thinner relative to control eyes after 1 year (P < 0.001), where both superficial anterior and subbasal nerve diameter did not change relative to control eyes. CONCLUSIONS. The pattern of reinnervation within tissue-engineered corneal substitutes has been quantified in vivo. Innervation proceeded rapidly in the deep anterior stroma, followed by repopulation of more superficial regions. One year after surgery, nerve density within the tissue-engineered cornea increased or remained unchanged relative to controls in all corneal regions examined. Copyright © Association for Research in Vision and Ophthalmology.

  • 23.
    Landsend, Erlend C. S.
    et al.
    Oslo Univ Hosp, Norway; Univ Oslo, Norway.
    Pedersen, Hilde R.
    Univ South Fastern Norway, Norway.
    Utheim, Oygunn A.
    Oslo Univ Hosp, Norway; Univ Oslo, Norway.
    Rueegg, Corina S.
    Oslo Univ Hosp, Norway.
    Baraas, Rigmor C.
    Univ South Fastern Norway, Norway.
    Lagali, Neil
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    Bragadottir, Ragnheidur
    Oslo Univ Hosp, Norway; Univ Oslo, Norway.
    Moe, Morten C.
    Oslo Univ Hosp, Norway; Univ Oslo, Norway.
    Utheim, Tor P.
    Oslo Univ Hosp, Norway; Stavanger Univ Hosp, Norway; Univ Bergen, Norway; Sorlandet Hosp, Norway.
    Characteristics and Utility of Fundus Autofluorescence in Congenital Aniridia Using Scanning Laser Ophthalmoscopy2019In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 60, no 13, p. 4120-4128Article in journal (Refereed)
    Abstract [en]

    PURPOSE. To investigate fundus autofluorescence (FAF) and other fundus manifestations in congenital aniridia. METHODS. Fourteen patients with congenital aniridia and 14 age- and sex-matched healthy controls were examined. FAF images were obtained with an ultra-widefield scanning laser ophthalmoscope. FAF intensity was quantified in the macular fovea and in a macular ring surrounding fovea and related to an internal reference within each image. All aniridia patients underwent an ophthalmologic examination, including optical coherence tomography and slitlamp biomicroscopy. RESULTS. Mean age was 28.4 +/- 15.0 years in both the aniridia and control groups. Fovea could be defined by subjective assessment of FAF images in three aniridia patients (21.4%) and in all controls (P = 0.001). Mean ratio between FAF intensity in the macular ring and fovea was 1.01 +/- 0.15 in aniridia versus 1.18 +/- 0.09 in controls (P = 0.034). In aniridia, presence of foveal hypoplasia evaluated by biomicroscopy correlated with lack of foveal appearance by subjective analyses of FAF images (P = 0.031) and observation of nystagmus (P = 0.009). CONCLUSIONS. Aniridia patients present a lower ratio between FAF intensity in the peripheral and central macula than do healthy individuals. Both subjective and objective analyses of FAF images are useful tools in evaluation of foveal hypoplasia in aniridia.

  • 24.
    Landsend, Erlend C. S.
    et al.
    Oslo Univ Hosp, Norway; Univ Oslo, Norway.
    Utheim, Oygunn A.
    Oslo Univ Hosp, Norway; Oslo Univ Hosp, Norway.
    Pedersen, Hilde R.
    Univ Coll Southeast Norway, Norway.
    Aass, Hans Christian D.
    Oslo Univ Hosp, Norway.
    Lagali, Neil
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    Dartt, Darlene A.
    Harvard Med Sch, MA USA.
    Baraas, Rigmor C.
    Univ Coll Southeast Norway, Norway.
    Utheim, Tor P.
    Oslo Univ Hosp, Norway; Oslo Univ Hosp, Norway; Stavanger Univ Hosp, Norway; Univ Bergen, Norway.
    The Level of Inflammatory Tear Cytokines is Elevated in Congenital Aniridia and Associated with Meibomian Gland Dysfunction2018In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 59, no 5, p. 2197-2204Article in journal (Refereed)
    Abstract [en]

    PURPOSE. To investigate the tear cytokine profile in congenital aniridia, and correlate cytokine levels with ophthalmologic findings. METHODS. We examined 35 patients with aniridia and 21 healthy controls. Tear fluid was collected with Schirmer I test and capillary tubes from each eye, and the concentration of 27 inflammatory cytokines determined using multiplex bead assay. Eyes of all participants were examined with tests for dry eye disease, including evaluation of meibomian glands (meibography). Differences in cytokine levels between the two groups were analyzed, and correlations between cytokine concentrations and ophthalmologic findings in the aniridia group investigated. RESULTS. The concentrations of six tear cytokines were significantly higher in aniridia patients than controls in both eyes, and included interleukin 1 beta (IL-1 beta), IL-9, IL-17A; eotaxin; basic fibroblast growth factor (bFGF/FGF2); and macrophage inflammatory protein 1 alpha (MIP-1 alpha/ CCL3). The ratio between the anti-inflammatory IL-1RA and the proinflammatory IL-1 beta was significantly lower in patients than controls in both eyes (P = 0.005 right eye and P = 0.001 left eye). Increasing concentration of IL-1 beta, IL-9, IL-17A, FGF2, and MIP-1 alpha correlated with parameters for meibomian gland dysfunction (MGD) in the aniridia group, including increasing atrophy of meibomian glands, and shorter break-up time of the tear film. CONCLUSIONS. A number of pro-inflammatory cytokines are significantly elevated in tear fluid from aniridia patients, and correlate with parameters for MGD in aniridia. Increased inflammation of the ocular surface may be a factor in the development of MGD in aniridia patients, and explain the high prevalence of MGD and dry eye disease in these patients.

  • 25. Liu, Yuwen
    et al.
    Gan, Lisha
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Ophthalmology.
    Carlsson, David J
    Fagerholm, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Ophthalmology. Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL.
    Lagali, Neil
    University of Ottawa.
    Watsky, Mitchell A
    Munger, Rejean
    Hodge, William G
    Priest, David
    Griffith, May
    A simple, cross-linked collagen tissue substitute for corneal implantation2006In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 47, no 5, p. 1869-1875Article in journal (Refereed)
    Abstract [en]

    PURPOSE. To develop a simple corneal substitute from crosslinked collagen. METHODS. Porcine type I collagen (10%, pH 5), was mixed with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and N-hydroxysuccinimide (NHS). The final homogenous solution was molded to corneal dimensions, cured, and then implanted into rabbits and minipigs by lamellar keratoplasty. The implants were followed for up to 6 months after surgery. Clinical examinations of the cornea included detailed slit lamp biomicroscopy, in vivo confocal microscopy, topography and esthesiometry for nerve function. Histopathologic examinations were also performed on rabbit corneas harvested after 6 months. RESULTS. Cross-linked collagen (refractive index, 1.35) had optical clarity superior to human corneas. Implanted into rabbit and porcine corneas, only 1 of 24 of the surgical corneas showed a slight haze at 6 months after surgery. All other implants showed no adverse reactions and remained optically clear. Topography showed a smooth surface and a profile similar to that of the contralateral nonsurgical eye. The implanted matrices promoted regeneration of corneal cells, tear film, and nerves. Touch sensitivity was restored, indicating some restoration of function. The corneas with implants showed no significant loss of thickness and demonstrated stable host- graft integration. CONCLUSIONS. Collagen can be adequately stabilized, using water soluble carbodiimides as protein cross-linking reagents, in the fabrication of corneal matrix substitutes for implantation. The simple cross-linking methodology would allow for easy fabrication of matrices for transplantation in centers where there is a shortage of corneas, or where there is need for temporary patches to repair perforations in emergency situations. Copyright © Association for Research in Vision and Ophthalmology.

  • 26. Merrett, Kimberley
    et al.
    Fagerholm, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    McLaughlin, Christopher R.
    Univ Ottawa, Dept Cellular & Mol Med, Ottawa, ON, Canada.
    Dravida, Subhadra
    Lagali, Neil
    University of Ottawa.
    Shinozaki, Naoshi
    Tokyo Dent Coll, Cornea Ctr & Eye Bank, Chiba, Japan.
    Watsky, Mitchell A.
    Univ Tennessee, Ctr Hlth Sci, Dept Physiol, Memphis, TN 38163 USA.
    Munger, Rejean
    Kato, Yasuhiro
    Tokyo Dent Coll, Cornea Ctr & Eye Bank, Chiba, Japan.
    Li, Fengfu
    Marmo, Christopher J.
    CooperVision Inc, Pleasanton, CA USA.
    Griffith, May
    Univ Ottawa, Dept Cellular & Mol Med, Ottawa, ON, Canada.
    Tissue-engineered recombinant human collagen-based corneal substitutes for implantation: Performance of type I versus type III collagen2008In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 49, no 9, p. 3887-3894Article in journal (Refereed)
    Abstract [en]

    PURPOSE. To compare the efficacies of recombinant human collagens types I and III as corneal substitutes for implantation. METHODS. Recombinant human collagen (13.7%) type I or III was thoroughly mixed with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide. The final homogenous solution was either molded into sheets for in vitro studies or into implants with the appropriate corneal dimensions for transplantation into minipigs. Animals with implants were observed for up to 12 months after surgery. Clinical examinations of the cornea included detailed slit lamp biomicroscopy, in vivo confocal microscopy, and fundus examination. Histopathologic examinations were also performed on corneas harvested after 12 months. RESULTS. Both cross-linked recombinant collagens had refractive indices of 1.35, with optical clarity similar to that in human corneas. Their chemical and mechanical properties were similar, although RHC-III implants showed superior optical clarity. Implants into pig corneas over 12 months show comparably stable integration, with regeneration of corneal cells, tear film, and nerves. Optical clarity was also maintained in both implants, as evidenced by fundus examination. CONCLUSIONS. Both RHC-I and -III implants can be safely and stably integrated into host corneas. The simple cross-linking methodology and recombinant source of materials makes them potentially safe and effective future corneal matrix substitutes.

  • 27.
    Mukwaya, Anthonny
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Mirabelli, Pierfrancesco
    Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    Lennikov, Anton
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Univ Missouri, MO USA.
    Thangavelu, Muthukumar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Chonbuk Natl Univ, South Korea.
    Jensen, Lasse
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology.
    Peebo, Beatrice
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    Lagali, Neil
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping. Sorlandet Hosp Arendal, Norway.
    Repeat Corneal Neovascularization is Characterized by More Aggressive Inflammation and Vessel Invasion Than in the Initial Phase2019In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 60, no 8, p. 2990-3001Article in journal (Refereed)
    Abstract [en]

    Purpose: Treatment of corneal neovascularization can lead to vessel regression and recovery of corneal transparency. Here, we examined the response of the cornea to a repeated stimulus after initial vessel regression comparing the second wave of neovascularization with the first.

    Methods: Corneal neovascularization was induced by surgical suture placement in the rat cornea for 7 days, followed by suture removal and a 30-day regression period. Corneas were then re-sutured and examined for an additional 4 days. Longitudinal slit-lamp imaging, in vivo confocal microscopy, and microarray analysis of global gene expression was conducted to assess the inflammatory and neovascularization response. Inhibitory effect of topical dexamethasone for repeat neovascularization was assessed.

    Results: After initial robust neovascularization, 30 days of regression resulted in the recovery of corneal transparency; however, a population of barely functional persistent vessels remained at the microscopic level. Upon re-stimulation, inflammatory cell invasion, persistent vessel dilation, vascular invasion, and gene expression of VegfaIl1βIl6Ccl2Ccl3, and Cxcl2 all doubled relative to initial neovascularization. Repeat neovascularization occurred twice as rapidly as initially, with activation of nitric oxide and reactive oxygen species, matrix metalloproteinase, and leukocyte extravasation signaling pathways, and suppression of anti-inflammatory LXR/RXR signaling. While inhibiting initial neovascularization, a similar treatment course of dexamethasone did not suppress repeat neovascularization.

    Conclusions: Persistent vessels remaining after the initial resolution of neovascularization can rapidly reactivate to facilitate more aggressive inflammation and repeat neovascularization, highlighting the importance of achieving and confirming complete vessel regression after an initial episode of corneal neovascularization.

  • 28.
    Nilsson, S F E
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Pharmacology.
    Mäepea, O
    Alm, A
    Narfström, K
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Internal Medicine.
    Ocular blood flow and retinal metabolism in abyssinian cats with hereditary retinal degeneration2001In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 42, no 5, p. 1038-1044Article in journal (Refereed)
    Abstract [en]

    Purpose. To investigate if retinal blood flow decreases with progression of the disease in Abyssinian cats with progressive retinal atrophy (PRA), to examine if the choroidal blood flow was affected by the disease, and to determine the uptake of glucose and formation of lactate in the outer retina. Methods. Local blood flow in different parts of the eye was determined with radioactive microspheres, in 9 normal cats and in 10 cats at different stages of PRA. Three blood flow determinations were made in each animal, during control conditions, after IV administration of indomethacin and after subsequent administration of Nw-nitro-L-arginine (L-NA). Blood samples from a choroidal vein and a femoral artery were collected to determine the retinal formation of lactate and uptake of glucose. Results. In Abyssinian cats with PRA (n = 10), the retinal blood flow was significantly (P = 0.01) lower than in normal cats (n = 9) during control conditions, 6.4 ▒ 1.7 compared with 14.1 ▒ 1.9 g min-1 (100 g)-1. The vascular resistance in the iris and ciliary body was significantly higher in the cats at a late stage of PRA, both compared with normal cats and to cats at an early stage of the disease, whereas the choroidal vascular resistance was not significantly affected. Indomethacin had no effect on ocular blood flows in normal cats, but in cats with PRA, iridal blood flow was more than doubled after indomethacin. The retinal formation of lactate was significantly (P = 0.001) lower in cats with PRA than in normal cats, 0.111 ▒ 0.035 (n = 8) compared with 0.318 ▒ 0.024 (n = 8) ╡mol rain-1. The uptake of glucose was not significantly different in cats with PRA. Conclusions. Retinal blood flow is severely decreased in Abyssinian cats at a late stage of retinal degeneration, whereas the choroidal microcirculation is not significantly affected by the disease. At a late stage of retinal degeneration, vascular resistance in the iris is significantly increased, which at least in part could be caused by cyxlooxygenase products.

  • 29.
    Nilsson, Siv
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Pharmacology.
    Drecoll, E
    Lütjen-Drecoll, E
    Toris, C
    Krauss, A
    Kharlamb, A
    Nieves, A
    Guerra, T
    Woodward, D
    The prostanoid EP2 receptor agonist butaprost increases uveoscleral outflow in the cynomolgus monkey2006In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 47, no 9, p. 4042-4049Article in journal (Refereed)
    Abstract [en]

    PURPOSE. To investigate the ocular hypotensive effect of the prostanoid EP2 receptor agonist butaprost and to establish its mechanism of action. METHODS. All experiments were performed in cynomolgus monkeys after topical application of butaprost (0.1%). The effects of butaprost on aqueous humor flow were determined by fluorophotometry. Total outflow facility was measured by the two-level, constant-pressure perfusion method, and uveoscleral outflow was determined by perfusion of FITC-labeled dextran through the anterior chamber. Effects on ocular morphology were studied after tissue fixation with transcardial perfusion by paraformaldehyde and immersion fixation of the globe, in animals subjected to long-term treatment with butaprost. Conscious ocular normotensive monkeys and monkeys with unilateral ocular hypertension were used for intraocular pressure (IOP) studies. RESULTS. Butaprost had no significant effect on aqueous humor flow or total outflow facility in ocular normotensive monkeys. Uveoscleral outflow was significantly higher in the butaprost treated eyes than in vehicle treated eyes, 1.03 ± 0.20 vs. 0.53 ± 0.18 μL · min-1. After a 1-year treatment with butaprost, the morphology of the ciliary muscle was changed, showing increased spaces between ciliary muscle bundles and the apparent formation of new outflow channels. In many instances, changes were observed in the trabecular meshwork as well. Butaprost, in a single 0.1% dose, decreased IOP significantly in ocular normotensive monkeys and reduced IOP in laser-induced glaucomatous monkey eyes to the same level as that in the ocular normotensive contralateral eyes. CONCLUSIONS. The prostanoid EP2 receptor agonist butaprost appears to lower IOP by increasing uveoscleral outflow, according to both physiological and morphologic findings. Although the prostanoid EP2 receptor is structurally and functionally distinct from the FP receptor, the effects of EP2 and FP receptor stimulation on aqueous humor outflow are similar. Copyright © Association for Research in Vision and Ophthalmology.

  • 30.
    Ong, Jeb A.
    et al.
    Maisonneuve Rosemt Hospital, Canada; University of Montreal, Canada.
    Auvinet, Edouard
    University of Montreal, Canada.
    Forget, Karolyn J.
    Maisonneuve Rosemt Hospital, Canada.
    Lagali, Neil
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    Fagerholm, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    Griffith, May
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Maisonneuve Rosemt Hospital, Canada.
    Meunier, Jean
    University of Montreal, Canada; University of Montreal, Canada.
    Brunette, Isabelle
    Maisonneuve Rosemt Hospital, Canada; University of Montreal, Canada.
    3D Corneal Shape After Implantation of a Biosynthetic Corneal Stromal Substitute2016In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 57, no 6, p. 2355-2365Article in journal (Refereed)
    Abstract [en]

    PURPOSE. The current and projected shortage of transplantable human donor corneas has prompted the development of long-term alternatives to human donor tissue for corneal replacement. The biosynthetic stromal substitutes (BSS) characterized herein represent a potentially safe alternative to donor organ transplantation for anterior corneal stromal diseases. The goal of this phase 1 safety study was to characterize the three-dimensional (3D) corneal shape of the first 10 human patients implanted with a BSS and assess its stability over time. METHODS. Ten patients underwent anterior lamellar keratoplasty using a biosynthetic corneal stromal implant for either advanced keratoconus or central corneal scarring. Surgeries were performed at Linkoping University Hospital, between October and November 2007. Serial corneal topographies were performed on all eyes up to a 4-year follow-up when possible. Three-dimensional shape average maps were constructed for the 10 BSS corneas and for 10 healthy controls. Average 3D shape corneal elevation maps, difference maps, and statistics maps were generated. RESULTS. The biosynthetic stromal substitutes implants remained stably integrated into the host corneas over the 4-year follow-up period, without signs of wound dehiscence or implant extrusion. The biosynthetic stromal substitutes corneas showed steeper surface curvatures and were more irregular than the healthy controls. CONCLUSIONS. Corneal astigmatism and surface steepness were observed 4 years after BSS implantation, while the implants remained stably integrated in the host corneas. Future studies will indicate if biomaterials technology will allow for the optimization of postoperative surface irregularity after anterior stromal replacement, a new window of opportunity that is not available with traditional corneal transplantation techniques.

  • 31.
    Parissi, Marlen
    et al.
    Oslo University Hospital, Norway.
    Karanis, Georgios
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Randjelovic, Stefan
    Norwegian Dry Eye Clin, Norway.
    Germundsson, Johan
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Poletti, Enea
    University of Padua, Italy.
    Ruggeri, Alfredo
    University of Padua, Italy.
    Paaske Utheim, Tor
    Oslo University Hospital, Norway.
    Lagali, Neil
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    Standardized Baseline Human Corneal Subbasal Nerve Density for Clinical Investigations With Laser-Scanning in Vivo Confocal Microscopy2013In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 54, no 10, p. 7091-7102Article in journal (Refereed)
    Abstract [en]

    Purpose. We established a baseline value for central corneal subbasal nerve density in a large, healthy cohort.

    Methods. A total of 106 healthy volunteers (207 eyes) underwent full ophthalmic examination, including laser-scanning in vivo confocal microscopy (IVCM) of the central cornea. Images of the corneal subbasal nerve plexus were acquired and analyzed based on defined criteria. Nerve tracing was performed by two human observers and by a fully automated method. Subbasal nerve density was stratified by eye, observer, tracing method, calculation method, and age group. Association of nerve density with age was examined by linear regression and population distribution was examined by nonlinear regression.

    Results. We analyzed 892 distinct, high quality images of the subbasal nerve plexus (mean, 4.3 images/eye) from 207 eyes. An overall mean central subbasal nerve density of 19 mm/mm2 was found in 106 subjects aged 15 to 88 years, independent of eye, sex, or nerve tracing method, while the SD was a consistent 4 to 5 mm/mm2. Subbasal nerve density followed a normal Gaussian distribution, and correlated negatively with age, with a mean decline of 0.25% to 0.30% per year, independent of eye, observer, or nerve tracing method. Moreover, the use of automated tracing techniques and randomized sampling may improve the speed and reproducibility of subbasal nerve density assessment for clinical applications.

    Conclusions. A baseline human corneal subbasal nerve density has been determined by laser-scanning IVCM using rigorous methods. The methods and results could aid in the future assessment of corneal nerves in various patient populations.

  • 32.
    Podskochy, Alexander
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology . Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    Koulikovska, Marina
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology . Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    Fagerholm, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology . Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    Expression of alpha-smooth muscle actin during wound healing in UVR-exposed rabbit corneas2003In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 44, p. 889-Conference paper (Other academic)
  • 33.
    Podskochy, Alexander
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology . Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    Koulikovska, Marina
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology . Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    Fagerholm, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology . Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    van der Ploeg, I
    Expression of proteoglycan biglycan in UV-exposed rabbit corneas.2001In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 42, no 4, p. 4769-Conference paper (Other academic)
  • 34.
    Schmid, Eduard
    et al.
    Department of Opthalmology Insbruch Medical University.
    Leisterer, Johannes
    Department of Pharmacology Insbruch Medical University.
    Doblinger, Alfred
    Department of Pharmacology Medical University of Insbruch.
    Laslop, Andrea
    Department of Pharmacology Medical University of Insbruch.
    Fischer-Colibrie, Reiner
    Department of Pharmacology Medical University of Insbruch.
    Humpel, Christian
    Laboratory of Psychiatry Medical University of Insbruch.
    Theodorsson, Elvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Teuchner, Barbara
    Department of Opthalmology Medical University of Insbruch.
    Lalehabbasi, Djavad
    Department of Opthalmology Medical Uiversity of Insbruch.
    Dragosits, Ernst
    Department of Opthalmology Medical University of Insbruch.
    Kunze, Christian
    Department of Opthalmology Medical University of Insbruch.
    Philipp, Wolfgang
    Department of Opthalmology Medical University of Insbruch.
    Göttinger, Wolfgang
    Department of Opthalmology Medical University of Insbruch.
    Troger, Josef
    Department of Opthalmology Medical University of Insbruch.
    Neurokinin A is a main constituent of sensory neurons innervating the anterior segment of the eye2005In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 46, no 1, p. 268-274Article in journal (Refereed)
    Abstract [en]

    PURPOSE. To study the innervation pattern of the anterior segment of the eye by neurokinin (NK)-A-immunoreactive nerves and to determine their sensory origin. METHODS. The presence and distribution of NKA was examined in human eyes by radioimmunoassay and immunofluorescence. The source of nerves was determined by measuring the concentration of NKA in the trigeminal ganglion (TG) in comparison with that of the classic sensory peptides substance P (SP) and calcitonin gene-related peptide (CGRP) and in eye tissues in capsaicin-pretreated rats versus control subjects. The NKA-like immunoreactivities were further characterized by reversed phase HPLC in the rat TG and the human iris- ciliary body complex. The presence of γ-PPT-A mRNA was studied in the rat TG by in situ hybridization. RESULTS. The levels of NKA in human eye tissues were approximately 10 times higher than those of SP but lower than those of CGRP. Nerve fibers were visualized in the cornea, the trabecular meshwork, the iridial stroma, and, prominently, in the sphincter muscle, the ciliary body stroma and muscle and processes, and the choroidal stroma and surrounding blood vessels. In the rat TG, the concentration of NKA was approximately five times higher than that of SP. Capsaicin led to a >60% decrease of the concentration of the peptide in the rat TG and rat eye tissues except for the retina. NKA-like immunoreactivities were present in a single peak corresponding to synthetic NKA, both in the rat TG and in the human iris- ciliary body complex, and numerous ganglion cells of small size were labeled by a γ-PPT-A probe in the rat TG. CONCLUSIONS. The present results clearly demonstrate that NKA is a main constituent of sensory neurons innervating the anterior segment of the eye. The presence of the peptide in C fibers in ocular tissues indicates a participation in sensory transmission and an involvement in the irritative response in the eye, a model for neurogenic inflammation in lower mammals.

  • 35.
    Sundelin, Staffan
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology . Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    Nilsson, SEG
    Brunk, Ulf
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Pharmacology .
    Lipofuscin accumulation in cultured retinal pigment epithelial cells is dependent on the melanin content2000In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 41, no 4, p. 4472B419-Conference paper (Other academic)
  • 36.
    Terman, Alexei
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Pathology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Clinical Genetics.
    Brunk, Ulf
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Pathology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Clinical Genetics.
    Is lipofuscin eliminated from cells?1999In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 40, p. 2463-2464Article in journal (Refereed)
1 - 36 of 36
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