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Deniz Hos, Jens Horstmann, Sebastian E Siebelmann, Franziska Bucher, Philipp Steven, Felix Bock, Reza Dana, Claus Cursiefen; Transient and Selective Ingrowth of Lymphatic Vessels into the Cornea after Incision Injury. Invest. Ophthalmol. Vis. Sci. 2016;57(12):1257.
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© 2017 Association for Research in Vision and Ophthalmology.
Corneal lymphangiogenesis contributes to several ocular pathologies such as dry eye, ocular allergy and corneal graft rejection. However, a physiological role for corneal lymphangiogenesis, e.g. during corneal wound healing, has not been described so far. Therefore, aim of this study was to evaluate whether corneal lymphangiogenesis occurs during the physiological healing course after a perforating corneal incision injury.
A central perforating corneal incision was performed in C57BL/6 mice. Afterwards, corneal opacity and edema were scored clinically and analyzed by optical coherence tomography (OCT). In order to investigate their relationship to corneal hem- and lymphangiogenesis, blood and lymphatic vessels were analyzed in whole mounts stained with CD31 and LYVE-1. Real-time PCR was performed to analyze gene expression of the lymphangiogenic ligands VEGF-C and VEGF-D and the corresponding receptor VEGFR-3.
Injured corneas developed opacity and edema, detectable as an increase of central corneal thickness (CCT), which peaked in the first two weeks after incision injury (mean CCT in uninjured: 90.1µm; after 1 week: 147.9µm, p<0.01; after 2 weeks: 165.6µm, p<0.01) and then gradually decreased until corneas became clear after 4 weeks (mean CCT after 4 weeks: 125.4µm, p>0.05). In addition, incision injury resulted in selective ingrowth of lymphatic, but not blood vessels, into the cornea. Corneal lymphangiogenesis peaked within the first two weeks (mean lymphvascularized area in uninjured: 2.09%; after 1 week: 7.35%, p<0.001; after 2 weeks: 6.87%, p<0.01) and then regressed (mean lymphvascularized area after 4 weeks: 3.45%, p>0.05). Furthermore, ingrowth of corneal lymphatic vessels was accompanied by upregulated gene expression of VEGF-C (x2.5 after 1 week; x2.0 after 2 weeks; x1.7 after 4 weeks; all p-values <0.01), VEGF-D (x2.0 after 1 week, p<0.01; x1.0 after 2 weeks, p>0.05; x1.1 after 4 weeks, p>0.05) and VEGFR-3 (x14.4 after 1 week, p<0.001; x1.7 after 2 weeks, p<0.05; x3.4 after 4 weeks, p<0.01).
A central perforating incision injury leads to transient and selective ingrowth of lymphatic vessels into the cornea, which points to a putative physiological role of lymphangiogenesis during corneal wound healing.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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