Simultaneous Onset of Corneal Lymphangiogenesis and Angiogenesis in the Mouse Model of Inflammatory Corneal Neovascularization
Cursiefen C.1, Jackson D.2, Dana M. R.1, Streilein J. W.1
1Dept. of Ophthalmology, Schepens Eye Research Institute, Harvard Medical School, Boston/USA; 2Institute of Molecular Medicine Oxford, MRC Human Immunology Unit, Oxford/UK
Purpose: Neovascularization of the cornea not only reduces visual acuity but also creates a high-risk bed for penetrating keratoplasty. We determined if lymphangiogenesis accompanies hemangiogenesis in a murine model of inflammatory corneal neovascularization.
Method: Three 11/0 intrastromal sutures were placed in eyes of BALB/c mice at a defined distance from the limbus. Corneal blood- and lymphangiogenesis were quantified by slit-lamp examination, and by immunofluorescence microscopy and morphometry using CD31 as a panendothelial and LYVE-1 as a lymphatic endothelial-specific marker in corneal flat mounts.
Results: CD31+/LYVE-1+ lymphatic vessels were consistently observed to accompany new CD31+/LYVE-1- corneal blood vessels sprouting out from limbal vascular arcades, starting within the first days, and being easily detectable biomicroscopically at day 3. Initially, lymphatic vessels preceeded blood vessels. Lymphatic vessels and blood vessels persisted for up to 6 months after suture removal. Neutrophils were conspicuous during early angiogenesis.
Conclusions: Lymphangiogenesis is an ea
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