Lebecetin, a C-type lectin, inhibits choroidal and retinal neovascularization

Abstract

Angiogenesis is a cause of visual impairment and blindness in the wet form of age-related macular degeneration and in ischemic retinopathies. Current therapies include use of anti-VEGF agents to reduce choroidal neovascularization (CNV) and edema. These treatments are effective in most cases, but spontaneous or acquired resistance to anti-VEGF and possible adverse effects of long-term VEGF inhibition in the retina and choroid highlight a need for additional alternative therapies. Integrins avb3 and avb5, which regulate endothelial cell proliferation and stabilization, have been implicated in ocular angiogenesis. Lebecetin (LCT) is a 30-kDa heterodimeric C-type lectin that is isolated fromMacrovipera lebetina venom and interactswith a5b1- and av-containing integrins.WepreviouslyshowedthatLCTinhibitshumanbrainmicrovascular endothelial cell adhesion,migration, proliferation, and tubulogenesis. To evaluate the inhibitory effect of LCT on ocular angiogenesis,we cultured aortic and choroidal explants in the presence of LCTand analyzed the effect of LCTonCNVin themouseCNVmodel and on retinalneovascularizationinthe oxygen-induced retinopathymodel.Our data demonstrate that a single injection ofLCTefficiently reducedCNVandretinalneovascularizationinthesemodels.