Inhibition of Corneal Lymphangiogenesis and Angiogenesis after Low-risk Keratoplasty using VEGF TrapR1R2 improves Transplant Survival
Cursiefen C.1, Chen L.1, Jackson D.2, Rudge J.S.3, Wiegand S.J.3, 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; 3Regeneron Pharmaceuticals Inc., Tarrytown/USA
Purpose: Neovascularization of the cornea occurs in about 50% of patients after low-risk corneal transplantation. We sought to determine whether inhibition of angiogenesis and lymphangiogenesis occurring after transplantation improves graft survival.
Method: Using the mouse model of low-risk corneal transplantation, C57BL6 donor grafts (diameter 2 mm) were placed in avascular recipient beds of BALB/c mice aged 6-8 weeks. One group of BALB/c mice was treated intraperitoneally with 12.5 mg/kg VEGF TrapR1R2 (a chimeric protein consisting of VEGF receptor 1 and 2 domains coupled to a Fc-fragment) on day 1 and 8 after transplantation or with human Fc-protein alone (control). Graft survival was evaluated using slit-lamp microscopy until week 8. Corneal blood and lymph angiogenesis 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.
Results: In mice treated wit
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