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Bourghardt Peebo, Beatrice
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Publications (10 of 16) Show all publications
Mirabelli, P., Bourghardt Peebo, B., Xeroudaki, M., Koulikovska, M. & Lagali, N. (2014). Early effects of dexamethasone and anti-VEGF therapy in an inflammatory corneal neovascularization model. Experimental Eye Research, 125, 118-127
Open this publication in new window or tab >>Early effects of dexamethasone and anti-VEGF therapy in an inflammatory corneal neovascularization model
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2014 (English)In: Experimental Eye Research, ISSN 0014-4835, E-ISSN 1096-0007, Vol. 125, p. 118-127Article in journal (Refereed) Published
Abstract [en]

Inflammatory angiogenesis is the pathogenic mechanism of various sight-threatening eye diseases, among them corneal neovascularization. Current treatment options include steroids which have undesirable side effects, or anti-VEGF which has only limited efficacy. In an inflammatory environment, however, angiogenesis can be stimulated by numerous factors not directly targeted by anti-VEGF therapy. The aim of this study was to induce corneal inflammation leading to angiogenesis, and investigate the early, differential effects of steroid and anti-VEGF therapy at the cellular, tissue, and gene expression levels. Fifty-two Wistar rats received a single intrastromal corneal suture to induce a controlled inflammatory angiogenic response. Rats were subsequently treated with dexamethasone, rat specific anti-VEGF, or goat IgG (control), topically 4 times daily for 7 days. In vivo confocal microscopy of the cornea was performed longitudinally from 5 h up to 7 d to investigate morphology at the cellular and tissue-level. In vivo photographic vessel analysis and immunohistochemistry were also performed. RT-PCR for VEGF-A, FGF-2, IL-6, TNF-alpha, CXCL2, CCL2, CCL3 and DLL4 was performed at 24 h, and for VEGF-A, IL-6, TNF-alpha, FGF-2, CXCL2, CCL2, and CCL3 at 7 days. Early infiltration of CD11b + myeloid cells into the cornea at 5 h post-suture was delayed by both treatments relative to controls; however neither treatment was able to suppress accumulation of myeloid cells at day 2 or 7. Limbal vessel dilation was inhibited at 5 h by both treatments, but only dexamethasone showed sustained effect until day 2. Early macrophage recruitment was also suppressed by dexamethasone (but not by anti-VEGF) until day 2. Dexamethasone furthermore suppressed corneal neovascularization at day 7 by over 90%, whereas suppression by anti-VEGF was 14%. Despite differential suppression of vessel dilation, macrophage recruitment, and vascular invasion, anti-VEGF and dexamethasone both down-regulated VEGF-A and IL-6 expression at 24 h with sustained effect to 7 d. They also both down regulated FGF-2 and TNF-alpha at 24 h and CCL2 at 7 d. In conclusion, anti-angiogenic treatments influence early, pre-angiogenic tissue activity such as limbal vessel dilation, inflammatory cell infiltration of the stroma, and macrophage recruitment. Importantly, the differential effects of steroids and anti-VEGF treatment in suppressing neovascular growth could not be attributed to differential inhibition of several major angiogenic and inflammatory factors in the early pre-sprouting phase, including IL-6, VEGF-A, FGF-2, TNF-alpha, CCL2, CCL3, CXCL2, or DLL4.

Place, publisher, year, edition, pages
Elsevier, 2014
Keywords
angiogenesis; neovascularization; cornea; inflammation; dexamethasone; anti-VEGF; confocal microscopy; rat
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-110279 (URN)10.1016/j.exer.2014.06.006 (DOI)000340079300014 ()24933712 (PubMedID)
Note

Funding Agencies|Crown Princess Margaretas Foundation; County Council of Ostergotland; Swedish Research Council [2012-2472]

Available from: 2014-09-05 Created: 2014-09-05 Last updated: 2019-04-18Bibliographically approved
Wiklund, A. & Bourghardt Peebo, B. (2013). ACUTE EXUDATIVE POLYMORPHOUS VITELLIFORM MACULOPATHY IN A YOUNG WOMAN: PRESYMPTOMATIC FINDINGS AND 21-MONTH FOLLOW-UP. RETINAL Cases & Brief Reports, 7(2), 123-127
Open this publication in new window or tab >>ACUTE EXUDATIVE POLYMORPHOUS VITELLIFORM MACULOPATHY IN A YOUNG WOMAN: PRESYMPTOMATIC FINDINGS AND 21-MONTH FOLLOW-UP
2013 (English)In: RETINAL Cases & Brief Reports, ISSN 1935-1089, Vol. 7, no 2, p. 123-127Article in journal (Refereed) Published
Abstract [en]

Purpose: To describe ocular findings before and after the diagnosis of acute exudative polymorphous vitelliform maculopathy, in an otherwise healthy 28-year-old woman.

Methods: Case report with 21-months of follow-up. Fundus photography, optical coherence tomography, fluorescein angiography, indocyanine green angiography, and autofluorescence were used for imaging the retina. To examine retinal function, full-field electroretinogram, multifocal electroretinogram, electrooculography, and dark adaptometry were performed. Genetic analysis for mutations associated with Best disease was done.

Results: In the asymptomatic patient before diagnosis, white-yellow, drusen-like, subretinal depositions were found in both eyes. A few months later, the patient developed bilateral visual disturbances. Retinal examination at the acute phase revealed a characteristic pattern of multifocal white-yellow subretinal lesions in both posterior poles, imaged by ophthalmoscopy, fluorescein angiography, indocyanine green angiography, and optical coherence tomography. Additionally, electrooculography and dark adaptometry were abnormal. Full-field electroretinogram was normal, but multifocal electroretinogram revealed central depression of peak amplitudes. During the 21-month follow-up without any treatment, visual acuity recovered, electrooculography and dark adaptometry normalized, and the patient experienced one episode of relapse. Genetic studies excluded mutations in the bestrophin gene (BEST1).

Conclusion: Acute exudative polymorphous vitelliform maculopathy is still a condition of unknown origin, primarily affecting the pigment epithelium. Earlier reports have discussed whether the condition is inherited or acquired. In this report, the presymptomatic retinal findings in acute exudative polymorphous vitelliform maculopathy are described for the first time, indicating that a condition may be associated with primarily affected retinal pigment epithelium.

Keywords
acute exudative polymorphous vitelliform maculopathy, macular edema, presymptomatic findings, subretinal lesions
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-107177 (URN)10.1097/ICB.0b013e31825956dc (DOI)
Available from: 2014-06-09 Created: 2014-06-09 Last updated: 2018-07-03
Bourghardt Peebo, B., Fagerholm, P. & Lagali, N. (2013). An in Vivo Method for Visualizing Flow Dynamics of Cells within Corneal Lymphatics. Lymphatic Research and Biology, 11(2), 93-100
Open this publication in new window or tab >>An in Vivo Method for Visualizing Flow Dynamics of Cells within Corneal Lymphatics
2013 (English)In: Lymphatic Research and Biology, ISSN 1539-6851, E-ISSN 1557-8585, Vol. 11, no 2, p. 93-100Article in journal (Refereed) Published
Abstract [en]

Background: Monitoring the trafficking of specific cell populations within lymphatics could improve our understanding of processes such as transplant rejection and cancer metastasis. Current methods, however, lack appropriate image resolution for single-cell analysis or are incompatible with in vivo and longitudinal monitoring of lymphatics in their native state. We therefore sought to achieve high-resolution live imaging of the dynamic behavior of cells within lymph vessels in the rat cornea.

Methods/Results: Inflammatory angiogenesis was induced by suture placement in corneas of Wistar rats. Pre- and up to 3 weeks post-induction, corneas were noninvasively examined by laser-scanning in vivo corneal confocal microscopy (IVCM) using only endogenous contrast. Lymph vessels and the cells harbored therein were documented by still images, real-time video, and 3D confocal stack reconstruction of live tissue. In vivo, conjunctival and corneal lymphatics were morphologically distinct, those with corneal location being one-quarter the diameter of those in the conjunctiva (p<0.001). Cells were recruited to initially empty pre-existing lymph vessels during the first day of inflammation and maintained a dense occupation of vessels for up to 7 days. A diverse population of cells (diameter range: 1.5–27.5 μm) with varying morphology was observed, and exhibited variable flow patterns and were transported singly and in clusters of at least 2–9 adherent cells.

Conclusions: The in vivo microscopic technique presented enables lymph vessels and cell trafficking to be studied in high resolution in a minimally-perturbed physiologic milieu.

Place, publisher, year, edition, pages
Mary Ann Liebert, 2013
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-96496 (URN)10.1089/lrb.2012.0023 (DOI)000320503900006 ()
Available from: 2013-08-23 Created: 2013-08-20 Last updated: 2018-01-22
Lagali, N., Bourghardt Peebo, B., Germundsson, J., Edén, U., Danyali, R., Rinaldo, M. & Fagerholm, P. (2013). Laser-Scanning in vivo Confocal Microscopy of the Cornea: Imaging and Analysis Methods for Preclinical and Clinical Applications. In: Confocal Laser Microscopy: Principles and Applications in Medicine, Biology, and the Food Sciences. INTECH
Open this publication in new window or tab >>Laser-Scanning in vivo Confocal Microscopy of the Cornea: Imaging and Analysis Methods for Preclinical and Clinical Applications
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2013 (English)In: Confocal Laser Microscopy: Principles and Applications in Medicine, Biology, and the Food Sciences, INTECH, 2013Chapter in book (Other academic)
Place, publisher, year, edition, pages
INTECH, 2013
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-107179 (URN)10.5772/55216 (DOI)978-953-51-1056-9 (ISBN)
Available from: 2014-06-09 Created: 2014-06-09 Last updated: 2018-01-22
Bourghardt Peebo, B. (2012). Angiogenesis from a new perspective. (Doctoral dissertation). Linköping: Linköping University Electronic Press
Open this publication in new window or tab >>Angiogenesis from a new perspective
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Angiogenesis is the emergence of new blood and lymph vessels from existing ones. In the pathologic form it contributes to the onset and progression of numerous different human disorders such as cancer, inflammation, atherosclerosis and blinding eye diseases. There exist a number of models to study angiogenesis, both in vitro and in vivo, but there is no single perfect model so far. Consequently there is a need to develop new angiogenesis assays for evaluating blood and lymph vessel behaviour in different physiologic settings.

The aim of this thesis was to gain insight into in vivo angiogenesis introducing a new technique in an inflammatory corneal model. The method involved in vivo examination of the cornea and subsequent comparison of in vivo findings with ex vivo immunohistochemical analysis of the same tissue samples. An existing suture model for inflammatory angiogenesis in the cornea was modified for in vivo observations with a clinically-approved corneal confocal microscope.

In this thesis, corneal lymph vessels were characterized for the first time in vivo and findings from the experimental bench could be applied in a clinical setting, where presumed lymphatics were observed in a corneal transplant patient with rejection. Furthermore, the technique was extended to investigate time-lapse processes in sprouting and regressing capillaries, and led to a number of new observations. CD11b+ myeloid cells constitute the first bulk of infiltrating inflammatory cells and contribute to inflammatory sprouting and regression in numerous ways including pre-patterning of the corneal stroma and guiding of capillary sprouts. Newly formed hemangiogenic sprouts are perfused with a slow-moving fluid and have a lumen. In blood vessel regression, capillary remodeling occurred by abandonment of sprout tips in close association with macrophages and vascular loops formed by presumed intussusceptive angiogenesis. In addition, a network of pericyte- and endothelium-free basement membrane tubes was formed after desertion or degradation of vascular endothelium in former corneal capillaries.

In conclusion, we introduce a new in vivo technique for investigating angiogenesis in a corneal model were in vivo findings can be interpreted with ex vivo definitions of specific cell types by immunohistochemistry. Findings from pre-clinical experiments have been possible to apply in a clinical setting when examining patients with corneal pathology.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2012. p. 91
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1284
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-73137 (URN)978-91-7519-999-3 (ISBN)
Public defence
2012-01-20, Nils-Holger salen, Hälsouniversitetet, Campus US, Linköpings universitet, Linköping, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2011-12-19 Created: 2011-12-19 Last updated: 2019-12-10Bibliographically approved
Heintz, E., Wiréhn, A.-B., Bourghardt Peebo, B., Rosenqvist, U. & Levin, L.-Å. (2012). QALY weights for diabetic retinopathy: a comparison of health state valuations with HUI-3, EQ-5D, EQ-VAS, and TTO.. Value in Health, 15(3), 475-484
Open this publication in new window or tab >>QALY weights for diabetic retinopathy: a comparison of health state valuations with HUI-3, EQ-5D, EQ-VAS, and TTO.
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2012 (English)In: Value in Health, ISSN 1098-3015, E-ISSN 1524-4733, Vol. 15, no 3, p. 475-484Article in journal (Refereed) Published
Abstract [en]

Objective: To estimate quality-adjusted life-year weights for patients with diabetic retinopathy by using various methods and to investigate the empirical validity of the different measures.

Methods: The study population comprised 152 patients with diabetes in Östergötland County, Sweden. Participants were interviewed by telephone by using the time trade-off (TTO) method and a visual analogue scale (EQ-VAS) (direct valuations) as well as the EuroQol five-dimensional questionnaire (EQ-5D) and the health utilities index mark 3 (HUI-3) (indirect valuations). The quality-adjusted life-year weights were adjusted for potential confounders by using analysis of covariance. The empirical validity of the measures was examined by testing their ability to detect hypothetical differences between severity levels of diabetic retinopathy and by investigating the correlation between the measures and the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25).

Results: All measures detected significant differences in scores between patient groups classified according to visual impairment in the better eye (analysis of covariance, P < 0.05), but only HUI-3 and EQ-VAS detected significant differences between patient groups classified according to visual impairment or pathological progression in the worse eye. HUI-3 recorded a difference of 0.43 in values between normal vision and blindness in the better eye, which was more than twice the differences captured by the other measures (0.15–0.20). In addition, HUI-3 showed the highest correlation with NEI VFQ-25 (r = 0.54; P < 0.001).

Conclusions: In cost-utility analyses, the choice of quality-adjusted life-year measure may affect whether an intervention is considered cost-effective. Furthermore, if decisions are to be based on values from the general public, HUI-3 can be recommended for cost-utility analyses of interventions directed at diabetic retinopathy.

Place, publisher, year, edition, pages
Elsevier, 2012
Keywords
diabetes mellitus, diabetic retinopathy, EQ-5D, health utility index mark 3, NEI-VFQ-25, QALY, time trade-off, TTO, VAS
National Category
Health Care Service and Management, Health Policy and Services and Health Economy
Identifiers
urn:nbn:se:liu:diva-76280 (URN)10.1016/j.jval.2011.11.031 (DOI)000303940600011 ()22583458 (PubMedID)
Note

funding agencies|AstraZeneca AB||

Available from: 2012-04-02 Created: 2012-04-02 Last updated: 2017-12-07Bibliographically approved
Bourghardt Peebo, B., Fagerholm, P., Traneus-Rockert, C. & Lagali, N. (2011). Cellular level characterization of capillary regression in inflammatory angiogenesis using an in vivo corneal model. Angiogenesis, 14(3), 393-405
Open this publication in new window or tab >>Cellular level characterization of capillary regression in inflammatory angiogenesis using an in vivo corneal model
2011 (English)In: Angiogenesis, ISSN 0969-6970, E-ISSN 1573-7209, Vol. 14, no 3, p. 393-405Article in journal (Refereed) Published
Abstract [en]

In this study, we introduce a technique for repeated, microscopic observation of single regressing capillaries in vivo in inflamed murine corneas. Natural capillary regression was initiated by removal of inflammatory stimulus during an active pro-angiogenic phase, while the additional impact of anti-angiogenic treatment with triamcinolone or bevazicumab was investigated. Capillaries regressed naturally within 1 week and treatments did not further enhance the natural regression. Morphologically, early-phase regression was characterized by significant lumen narrowing and a significant reduction in CD11b+ myeloid cell infiltration of the extracellular matrix. By 1 week, vascular remodeling occurred concomitant with CD11b+CD68+KiM2R+ mature macrophage localization on capillary walls. Empty conduits without blood flow, positive for collagen IV and devoid of vascular endothelium and pericytes, were apparent in vivo and by 3 weeks were more numerous than perfused capillaries. By 3 weeks, macrophages aggregated around remaining perfused capillaries and were observed in apposition with degrading capillary segments. Abrupt termination of capillary sprouting in our regression model further revealed vascular endothelial abandonment of sprout tips and perfused capillary loop formation within a single angiogenic sprout, possibly as an intussusceptive response to cessation of the stimulus. Finally, we observed lumen constriction and macrophage localization on capillary walls in vivo in a clinical case of corneal capillary regression that paralleled findings in our murine model.

Place, publisher, year, edition, pages
Springer Verlag (Germany), 2011
Keywords
Inflammation, Capillary regression, In vivo confocal microscopy, Cornea
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-70325 (URN)10.1007/s10456-011-9223-3 (DOI)000293922300015 ()
Note
The original publication is available at www.springerlink.com: Beatrice Bourghardt Peebo, Per Fagerholm, Catharina Traneus-Rockert and Neil Lagali, Cellular level characterization of capillary regression in inflammatory angiogenesis using an in vivo corneal model, 2011, Angiogenesis, (14), 3, 393-405. http://dx.doi.org/10.1007/s10456-011-9223-3 Copyright: Springer Verlag (Germany) http://www.springerlink.com/Available from: 2011-09-02 Created: 2011-09-02 Last updated: 2018-01-22
Bourghardt Peebo, B., Fagerholm, P. & Lagali, N. (2011). Letter: In vivo confocal microscopy visualization of presumed lymph vessels in a case of corneal transplant rejection [Letter to the editor]. Clinical and Experimental Ophthalmology, 39(8), 832-834
Open this publication in new window or tab >>Letter: In vivo confocal microscopy visualization of presumed lymph vessels in a case of corneal transplant rejection
2011 (English)In: Clinical and Experimental Ophthalmology, ISSN 1442-6404, E-ISSN 1442-9071, Vol. 39, no 8, p. 832-834Article in journal, Letter (Other academic) Published
Abstract [en]

n/a

Place, publisher, year, edition, pages
Wiley-Blackwell, 2011
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-72259 (URN)10.1111/j.1442-9071.2011.02557.x (DOI)000296913900016 ()
Available from: 2011-11-24 Created: 2011-11-24 Last updated: 2018-01-22Bibliographically approved
Bourghardt Peebo, B., Fagerholm, P., Traneus-Rockert, C. & Lagali, N. (2011). Time-Lapse In Vivo Imaging of Corneal Angiogenesis: The Role of Inflammatory Cells in Capillary Sprouting. Investigative Ophthalmology and Visual Science, 52(6), 3060-3068
Open this publication in new window or tab >>Time-Lapse In Vivo Imaging of Corneal Angiogenesis: The Role of Inflammatory Cells in Capillary Sprouting
2011 (English)In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 52, no 6, p. 3060-3068Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Research in Vision and Opthalmology, 2011
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-69178 (URN)10.1167/iovs.10-6101 (DOI)000291100800026 ()
Note
Original Publication: Beatrice Bourghardt Peebo, Per Fagerholm, Catharina Traneus-Rockert and Neil Lagali, Time-Lapse In Vivo Imaging of Corneal Angiogenesis: The Role of Inflammatory Cells in Capillary Sprouting, 2011, INVESTIGATIVE OPHTHALMOLOGY and VISUAL SCIENCE, (52), 6, 3060-3068. http://dx.doi.org/10.1167/iovs.10-6101 Copyright: Research in Vision and Opthalmology http://www.arvo.org/Available from: 2011-06-17 Created: 2011-06-17 Last updated: 2018-01-22Bibliographically approved
Bourghardt Peebo, B., Fagerholm, P., Traneus-Rockert, C. & Lagali, N. (2010). Cellular-Level Characterization of Lymph Vessels in Live, Unlabeled Corneas by In Vivo Confocal Microscopy. Investigative Ophthalmology and Visual Science, 51(2), 830-835
Open this publication in new window or tab >>Cellular-Level Characterization of Lymph Vessels in Live, Unlabeled Corneas by In Vivo Confocal Microscopy
2010 (English)In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 51, no 2, p. 830-835Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Rockville, MD, United States: , 2010
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-53820 (URN)10.1167/iovs.09-4407 (DOI)000273704700030 ()
Available from: 2010-02-05 Created: 2010-02-05 Last updated: 2018-01-22Bibliographically approved
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