Endomucin knockout leads to delayed retinal vascular development and reduced ocular pathological neovascularization

Abstract

Endomucin (EMCN), an endothelial-specific glycocalyx component highly expressed in capillary and venous endothelium, plays a critical role in regulating VEGF receptor 2 (VEGFR2) endocytosis and downstream VEGF signaling. Using the first global EMCN knockout mouse model, we investigated the effects of EMCN deficiency on retinal vascularization during development and pathological angiogenesis. We found relatively high expression of EMCN in choroidal capillaries and retinal vasculature. Emcn-/- mice exhibited delayed retinal vascularization at postnatal day 5, with fewer tip cells and reduced vessel density. Ultrastructural examination revealed disrupted and reduced fenestrations in choroidal capillary endothelium. In an oxygen-induced retinopathy model, while Emcn-/- mice showed no significant difference in avascular area compared to Emcn+/+ mice at postnatal day 12, there was a significant reduction in neovascular tufts in Emcn-/- mice at postnatal day 17. Similarly, in a laser-induced choroidal neovascularization model, Emcn-/- mice showed a significant reduction in vascular leakage and lesion size. These findings suggest that EMCN plays a critical role in both vascular development and pathological neovascularization, highlighting its potential as a target for anti-angiogenic therapies.