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Lagali, N. S., Allgeier, S., Guimarães, P., Badian, R. A., Ruggeri, A., Köhler, B., . . . Rolandsson, O. (2017). Reduced Corneal Nerve Fiber Density in Type 2 Diabetes by Wide-Area Mosaic Analysis. Investigative Ophthalmology and Visual Science, 58(14), 6318-6327
Open this publication in new window or tab >>Reduced Corneal Nerve Fiber Density in Type 2 Diabetes by Wide-Area Mosaic Analysis
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2017 (English)In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 58, no 14, p. 6318-6327Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Association For Research In Vision And Ophthalmology, 2017
Keywords
Confocal microscopy, corneal nerves, subbasal nerve, diabetes mellitus
National Category
Ophthalmology
Identifiers
urn:nbn:se:liu:diva-146364 (URN)10.1167/iovs.17-22257 (DOI)000426781300038 ()29242906 (PubMedID)
Available from: 2018-04-07 Created: 2018-04-07 Last updated: 2019-01-22Bibliographically approved
Ong, J. A., Auvinet, E., Forget, K. J., Lagali, N., Fagerholm, P., Griffith, M., . . . Brunette, I. (2016). 3D Corneal Shape After Implantation of a Biosynthetic Corneal Stromal Substitute. Investigative Ophthalmology and Visual Science, 57(6), 2355-2365
Open this publication in new window or tab >>3D Corneal Shape After Implantation of a Biosynthetic Corneal Stromal Substitute
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2016 (English)In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 57, no 6, p. 2355-2365Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2016
Keywords
corneal implants; artificial cornea; corneal topography; corneal transplantation; keratoconus
National Category
Ophthalmology
Identifiers
urn:nbn:se:liu:diva-130307 (URN)10.1167/iovs.15-18271 (DOI)000378041700001 ()27136462 (PubMedID)
Note

Funding Agencies|Canadian Institutes of Health Research, Canada [MOP 106517]; Stem Cell Network, Ottawa, ON, Canada; FRQS Research in Vision Network, Montreal, QC, Canada; County Council of Ostergotland, Sweden; Charles-Albert Poissant Research Chair in Corneal Transplantation, University of Montreal, Canada

Available from: 2016-07-31 Created: 2016-07-28 Last updated: 2018-01-22
Rafat, M., Xeroudaki, M., Koulikovska, M., Sherrell, P., Groth, F., Fagerholm, P. & Lagali, N. (2016). Composite core-and-skirt collagen hydrogels with differential degradation for corneal therapeutic applications. Biomaterials, 83, 142-155
Open this publication in new window or tab >>Composite core-and-skirt collagen hydrogels with differential degradation for corneal therapeutic applications
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2016 (English)In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 83, p. 142-155Article in journal (Refereed) Published
Abstract [en]

Scarcity of donor tissue to treat corneal blindness and the need to deliver stem cells or pharmacologic agents to ensure corneal graft survival are major challenges. Here, new composite collagen-based hydrogels are developed as implants to restore corneal transparency while serving as a possible reservoir for cells and drugs. The composite hydrogels have a centrally transparent core and embedded peripheral skirt of adjustable transparency and degradability, with the skirt exhibiting faster degradation in vitro. Both core and skirt supported human epithelial cell populations in vitro and the skirt merged homogeneously with the core material to smoothly distribute a mechanical load in vitro. After in vivo transplantation in rabbit corneas over three months, composites maintained overall corneal shape and integrity, while skirt degradation could be tracked in vivo and non-invasively due to partial opacity. Skirt degradation was associated with partial collagen breakdown, thinning, and migration of host stromal cells and macrophages, while the central core maintained integrity and transparency as host cells migrated and nerves regenerated.

IMPACT:

This study indicates the feasibility of a collagen-based composite hydrogel to maintain corneal stability and transparency while providing a degradable peripheral reservoir for cell or substance release.

Keywords
Composite; Cornea; Degradation; Femtosecond laser; Keratoplasty; Porcine collagen
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:liu:diva-125229 (URN)10.1016/j.biomaterials.2016.01.004 (DOI)000371651700012 ()26773670 (PubMedID)
Note

Funding agencies:  Abbott Medical Optics Inc, Solna, Sweden

Available from: 2016-02-16 Created: 2016-02-16 Last updated: 2018-01-22
Ihnatko, R., Edén, U., Fagerholm, P. & Lagali, N. (2016). Congenital Aniridia and the Ocular Surface. OCULAR SURFACE, 14(2), 196-206
Open this publication in new window or tab >>Congenital Aniridia and the Ocular Surface
2016 (English)In: OCULAR SURFACE, ISSN 1542-0124, Vol. 14, no 2, p. 196-206Article in journal (Refereed) Published
Abstract [en]

Aniridia is a congenital pan-ocular disorder caused by haplo-insufficiency of Pax6, a crucial gene for proper development of the eye. Aniridia affects a range of eye structures, including the cornea, iris, anterior chamber angle, lens, and fovea. The ocular surface, in particular, can be severely affected by a progressive pathology termed aniridia-associated keratopathy (AAK), markedly contributing to impaired vision. The purpose of this review is to provide an update of the current knowledge of the genetic, clinical, micro-morphological, and molecular aspects of AAK. We draw upon material presented in the literature and from our own observations in large aniridia cohorts. We summarize signs and symptoms of AAK, describe current options for management, and discuss the latest research findings that may lead to better diagnosis and new treatment or prevention strategies for this debilitating ocular surface condition.

Place, publisher, year, edition, pages
ELSEVIER SCIENCE BV, 2016
Keywords
aniridia; aniridia-associated keratopathy; congenital aniridia; gene mutations; haplo-insufficiency; iris; Pax6 gene
National Category
Psychiatry
Identifiers
urn:nbn:se:liu:diva-128758 (URN)10.1016/j.jtos.2015.10.003 (DOI)000375222400012 ()
Note

Funding Agencies|Ogonfonden; Swedish Research Council [2012-2472]; Country of Ostergotland; Kronprinsessan Margaretas Arbetsnamnd

Available from: 2016-05-31 Created: 2016-05-30 Last updated: 2018-01-22
Parissi, M., Randjelovic, S., Poletti, E., Guimaraes, P., Ruggeri, A., Fragkiskou, S., . . . Lagali, N. (2016). Corneal Nerve Regeneration After Collagen Cross-Linking Treatment of Keratoconus A 5-Year Longitudinal Study. JAMA ophthalmology, 134(1), 70-78
Open this publication in new window or tab >>Corneal Nerve Regeneration After Collagen Cross-Linking Treatment of Keratoconus A 5-Year Longitudinal Study
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2016 (English)In: JAMA ophthalmology, ISSN 2168-6165, E-ISSN 2168-6173, Vol. 134, no 1, p. 70-78Article in journal (Refereed) Published
Abstract [en]

IMPORTANCE It is unknown whether a neurotrophic deficit or pathologic nerve morphology persists in keratoconus in the long term after corneal collagen cross-linking (CXL) treatment. Nerve pathology could impact long-term corneal status in patients with keratoconus. OBJECTIVE To determine whether CXL treatment of keratoconus results in normalization of subbasal nerve density and architecture up to 5 years after treatment. DESIGN, SETTING, AND PARTICIPANTS Observational study of 19 patients with early-stage keratoconus indicated for a first CXL treatment with longitudinal follow-up to 5 years postoperatively (examinations were performed from 2009 to 2015; analysis was performed from February to May 2015) and 19 age-matched healthy volunteers at a primary care center and a university hospital ophthalmology department. EXPOSURE The patients with keratoconus underwent standard epithelial-off UV-A/riboflavin CXL treatment with 30-minute UV-A exposure at 3mW/cm(2) irradiance. MAIN OUTCOMES AND MEASURES Central corneal subbasal nerve density and subbasal nerve architecture by use of laser-scanning in vivo confocal microscopy; subbasal nerve analysis by 2 masked observers and by use of a fully automated method; wide-field mosaics of subbasal nerve architecture by use of an automated method; and ocular surface touch sensitivity by use of contact esthesiometry. RESULTS Mean (SD) age of the 19 patients with keratoconus was 27.5 (7.1) years (range, 19-44 years), and minimal corneal thickness was 428 (36) mu m (range, 372-497 mu m). Compared with the mean (SD) preoperative subbasal nerve density of 21.0 (4.2) mm/mm(2) in healthy corneas, the mean (SD) preoperative subbasal nerve density of 10.3 (5.6) mm/mm(2) in the corneas of patients with stage 1 or 2 keratoconus was reduced 51%(mean difference, 10.7 mm/mm(2) [95% CI, 6.8-14.6 mm/mm(2)]; P &lt; .001). After CXL, nerves continued to regenerate for up to 5 years, but nerve density remained reduced relative to healthy corneas at final follow-up (mean reduction, 8.5 mm/mm(2) [95% CI, 4.7-12.4 mm/mm(2)]; P &lt; .001) despite recovery of touch sensitivity to normal levels by 6 months. Preoperatively, more frequent nerve loops, crossings, and greater crossing angles were observed in the corneas of patients with keratoconus compared with healthy corneas. Postoperatively, the frequency of nerve looping increased, crossings were more frequent, and nerve tortuosity increased. Wide-field mosaics indicated persistent disrupted orientation of the regenerating subbasal nerves 5 years after CXL. CONCLUSIONS AND RELEVANCE Keratoconus is characterized by a neurotrophic deficit and altered nerve morphology that CXL treatment does not address, despite providing a positive biomechanical effect in the stroma. Given the widespread use of CXL in the management of patients with keratoconus, the progression of abnormal innervation after CXL should be recognized.

Place, publisher, year, edition, pages
AMER MEDICAL ASSOC, 2016
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-127289 (URN)10.1001/jamaophthalmol.2015.4518 (DOI)000372538200018 ()26562763 (PubMedID)
Note

Funding Agencies|Swedish Research Council [2012-2472]; Princess Margaretas Foundation for the Visually Impaired; Norwegian Research Council

Available from: 2016-04-20 Created: 2016-04-19 Last updated: 2018-01-22
Fostad, I. G., Eidet, J. R., Utheim, T. P., Raeder, S., Lagali, N., Messelt, E. B. & Dartt, D. A. (2016). Dry Eye Disease Patients with Xerostomia Report Higher Symptom Load and Have Poorer Meibum Expressibility. PLoS ONE, 11(5), e0155214
Open this publication in new window or tab >>Dry Eye Disease Patients with Xerostomia Report Higher Symptom Load and Have Poorer Meibum Expressibility
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2016 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 5, p. e0155214-Article in journal (Refereed) Published
Abstract [en]

The purpose of the study was to investigate if xerostomia (dry mouth) is associated with symptoms and signs of dry eye disease (DED). At the Norwegian Dry Eye Clinic, patients with symptomatic DED with different etiologies were consecutively included in the study. The patients underwent a comprehensive ophthalmological work-up and completed self-questionnaires on symptoms of ocular dryness (Ocular Surface Disease Index [OSDI] and McMonnies Dry Eye Questionnaire) and the Sjogrens syndrome (SS) questionnaire (SSQ). Three hundred and eighteen patients (52% women and 48% men) with DED were included. Patient demographics were: 0 to 19 years (1%), 20 to 39 (25%), 40 to 59 (34%), 60 to 79 (35%) and 80 to 99 (5%). Xerostomia, defined as "daily symptoms of dry mouth the last three months" (as presented in SSQ) was reported by 23% of the patients. Female sex was more common among patients with xerostomia (81%) than among non-xerostomia patients (44%; Pamp;lt; 0.001). Patients with xerostomia (60 +/- 15 years) were older than those without xerostomia (51 +/- 17; Pamp;lt; 0.001). The use of prescription drugs was more prevalent among xerostomia patients (65%) than among non-xerostomia patients (35%; Pamp;lt; 0.021; adjusted for age and sex). Patients with xerostomia had a higher OSDI score (19.0 +/- 10.0) than those without xerostomia (12.9 +/- 8.0; Pamp;lt; 0.001). Moreover, xerostomia patients had more pathological meibum expressibility (0.9 +/- 0.7) than those without xerostomia (0.7 +/- 0.8; P = 0.046). Comparisons of OSDI and ocular signs were performed after controlling for the effects of sex, age and the number of systemic prescription drugs used. In conclusion, xerostomia patients demonstrated a higher DED symptom load and had poorer meibum expressibility than non-xerostomia patients.

Place, publisher, year, edition, pages
PUBLIC LIBRARY SCIENCE, 2016
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:liu:diva-129167 (URN)10.1371/journal.pone.0155214 (DOI)000375676800123 ()27148875 (PubMedID)
Available from: 2016-06-13 Created: 2016-06-13 Last updated: 2018-01-22
Koulikovska, M., Rafat, M., Petrovski, G., Veréb, Z., Akhtar, S., Fagerholm, P. & Lagali, N. (2015). Enhanced Regeneration of Corneal Tissue Via a Bioengineered Collagen Construct Implanted by a Nondisruptive Surgical Technique. Tissue Engineering. Part A, 21(5-6), 1116-1130
Open this publication in new window or tab >>Enhanced Regeneration of Corneal Tissue Via a Bioengineered Collagen Construct Implanted by a Nondisruptive Surgical Technique
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2015 (English)In: Tissue Engineering. Part A, ISSN 1937-3341, E-ISSN 1937-335X, Vol. 21, no 5-6, p. 1116-1130Article in journal (Refereed) Published
Abstract [en]

Severe shortage of donor corneas for transplantation, particularly in developing countries, has prompted the advancement of bioengineered tissue alternatives. Bioengineered corneas that can withstand transplantation while maintaining transparency and compatibility with host cells, and that are additionally amenable to standardized low-cost mass production are sought. In this study, a bioengineered porcine construct (BPC) was developed to function as a biodegradable scaffold to promote corneal stromal regeneration by host cells. Using high-purity medical-grade type I collagen, high 18% collagen content and optimized EDC-NHS cross-linker ratio, BPCs were fabricated into hydrogel corneal implants with over 90% transparency and four-fold increase in strength and stiffness compared with previous versions. Remarkably, optical transparency was achieved despite the absence of collagen fibril organization at the nanoscale. In vitro testing indicated that BPC supported confluent human epithelial and stromal-derived mesenchymal stem cell populations. With a novel femtosecond laser-assisted corneal surgical model in rabbits, cell-free BPCs were implanted in vivo in the corneal stroma of 10 rabbits over an 8-week period. In vivo, transparency of implanted corneas was maintained throughout the postoperative period, while healing occurred rapidly without inflammation and without the use of postoperative steroids. BPC implants had a 100% retention rate at 8 weeks, when host stromal cells began to migrate into implants. Direct histochemical evidence of stromal tissue regeneration was observed by means of migrated host cells producing new collagen from within the implants. This study indicates that a cost-effective BPC extracellular matrix equivalent can incorporate cells passively to initiate regenerative healing of the corneal stroma, and is compatible with human stem or organ-specific cells for future therapeutic applications as a stromal replacement for treating blinding disorders of the cornea.

Place, publisher, year, edition, pages
Mary Ann Liebert, 2015
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:liu:diva-114699 (URN)10.1089/ten.tea.2014.0562 (DOI)000350549500025 ()25412075 (PubMedID)
Available from: 2015-03-03 Created: 2015-03-03 Last updated: 2018-01-22Bibliographically approved
Lagali, N., Poletti, E., Patel, D. V., McGhee, C. N. J., Hamrah, P., Kheirkhah, A., . . . Ruggeri, A. (2015). Focused Tortuosity Definitions Based on Expert Clinical Assessment of Corneal Subbasal Nerves. Investigative Ophthalmology and Visual Science, 56(9), 5102-5109
Open this publication in new window or tab >>Focused Tortuosity Definitions Based on Expert Clinical Assessment of Corneal Subbasal Nerves
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2015 (English)In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 56, no 9, p. 5102-5109Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2015
Keywords
subbasal nerve; plexus; in vivo confocal microscopy; tortuosity; corneal nerves
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-122543 (URN)10.1167/iovs.15-17284 (DOI)000362882800009 ()26241397 (PubMedID)
Note

uj

Available from: 2015-11-06 Created: 2015-11-06 Last updated: 2018-01-22
Koulikovska, M., Szymanowski, O., Lagali, N. & Fagerholm, P. (2015). Platelet Rich Plasma Prolongs Myofibroblast Accumulation in Corneal Stroma with Incisional Wound. Current Eye Research, 40(11), 1102-1110
Open this publication in new window or tab >>Platelet Rich Plasma Prolongs Myofibroblast Accumulation in Corneal Stroma with Incisional Wound
2015 (English)In: Current Eye Research, ISSN 0271-3683, E-ISSN 1460-2202, Vol. 40, no 11, p. 1102-1110Article in journal (Refereed) Published
Abstract [en]

Purpose: The purpose of this study was to determine whether platelet rich plasma (PRP) has an effect on corneal stromal cells in a rat model of wound healing following corneal incision. Materials and Methods: The effect of PRP on corneal wound healing in vivo was investigated in a corneal incision wound model in rats. 40 rats were wounded by deep corneal incision, and treated with either topically administered PRP (20 rats) or sodium chloride (20 rats). At 4 hours and 1, 3, and 5 days after incision, α-smooth muscle actin (α SMA), SMAD2 and SMAD3 expression and apoptosis in stromal cells were evaluated by immunohistochemistry, and IL-1β mRNA expression was evaluated by real time PCR.

Results: PRP treated corneas exhibited reduced stromal cell apoptosis at day 3 and day 5 (p = 0.038, and <0.001, respectively) relative to controls. Interleukin-1β mRNA expression, however, was unchanged in PRP treated corneas relative to controls. Topical PRP treatment resulted in a higher proportion of αSMA-positive myofibroblasts recruited to the wound site relative to control corneas. PRP did not affect activation of SMAD2 but activation of SMAD3 was significantly reduced at day 1 (p=0.001) and dramatically increased at day 5 (p=0.032).

Conclusions: PRP treatment resulted in suppressed stromal cell apoptosis followed by SMAD3 activation and a greater proportion of myofibroblasts present at the wound site. Suppression of stromal cell apoptosis after corneal wounding by use of a growth factor rich formulation may lead to myofibroblast accumulation by modulation of the TGF-β pathway.

Place, publisher, year, edition, pages
Taylor & Francis, 2015
Keywords
Platelet rich plasma, corneal wound healing, α-smooth muscle actin, apoptosis, keratocytes
National Category
Cell and Molecular Biology Medical Biotechnology
Identifiers
urn:nbn:se:liu:diva-114698 (URN)10.3109/02713683.2014.978478 (DOI)000369891500004 ()
Note

Funding agencies:Swedish Research Council, Konung Gustaf V:s och Drottning Victorias Frimurarestiftelse, County Council of Ostergotland 

Vid tiden för disputation förelåg publikationen endast som manuskript

Available from: 2015-03-03 Created: 2015-03-03 Last updated: 2018-01-22Bibliographically approved
Koulikovska, M., Szymanowski, O., Lagali, N. & Fagerholm, P. (2015). Topical Biglycan Modulates Stromal Cell Apoptosis in Corneal Incisional Wound Model.
Open this publication in new window or tab >>Topical Biglycan Modulates Stromal Cell Apoptosis in Corneal Incisional Wound Model
2015 (English)Manuscript (preprint) (Other academic)
Abstract [en]

Purpose: The purpose of this study was to determine whether exogenous topicallyapplied biglycan has an effect on corneal stromal cells during wound healing.

Methods: Enzyme-linked immunosorbent assay (ELISA) was used to determine the effect of biglycan on cell survival in vitro following IL-1β induced cell death. In a corneal incisional wound model, 40 rats were wounded and treated with either topically administered biglycan or sodium chloride (sham control). At 4 hours and 1, 2, and 5 days after incision, α-smooth muscle actin (SMA) expression and apoptosis in stromal cells were evaluated by immunohistochemistry.

Results: In vitro, biglycan significantly enhanced IL-1β-induced apoptosis of myofibroblasts (p = 0.038), but not corneal fibroblasts. Biglycan treated corneas exhibited reduced stromal cell apoptosis at 4 hours, day 1 and day 5 (p = 0.012, 0.040, and 0.048, respectively) and increased apoptosis at day 3 (p = 0.003) relative to controls. In wounded corneas, biglycan appeared to promote early accumulation of myofibroblasts and initiate an earlier subsequent apoptosis of these cells, relative to controls.

Conclusion: Biglycan appears to accelerate corneal wound healing in vivo by modulating myofibroblast apoptosis, resulting in removal of myofibroblasts that may otherwise compromise corneal transparency.

Keywords
Corneal wound healing; biglycan; keratocytes; IL-1β; α-SMA
National Category
Cell and Molecular Biology Medical Biotechnology
Identifiers
urn:nbn:se:liu:diva-114697 (URN)
Available from: 2015-03-03 Created: 2015-03-03 Last updated: 2018-01-22
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0003-1079-4361

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