Retinal VEGFA maintains the ultrastructure and function of choriocapillaris by preserving the endothelial PLVAP

Abstract

Fenestrations in choriocapillaris act as a window for molecular transports between the retina and choroid, and is crucial for maintaining visual function. Plasmalemma vesicle-associated protein (PLVAP) is essential for the development of endothelial fenestrations. There is little knowledge about how the choriocapillaris maintains the fenestrated endothelium. This study aimed to evaluate the role of vascular endothelial growth factor-A (VEGFA)-PLVAP axis in the maintenance of choroidal fenestrations using oxygen-induced retinopathy (OIR) model. In C57BL/6 J mice, the mice with OIR on postnatal day 12 (P12) presented thicker endothelium and less fenestration compared to the non-OIR mice. However, the OIR on 17 mice showed thinner endothelium with more fenestration compared to OIR on P12. In vivo angiography demonstrated the presence of hyperpermeable choroidal vessels on P17 in OIR mice. These dramatic changes in choriocapillaris were not observed in the BALB/cJ OIR model. The ultrastructural changes in the choriocapillaris were correlated with temporal variations in the expression of VEGFA and PLVAP. VEGFA stimulated expression of PLVAP in the choroidal endothelial cells. Loss of PLVAP disrupts the polarized structure of the choriocapillaris leading to retinal degeneration. These results indicate that the expression of retinal VEGFA is essential for maintaining the structure and function of choriocapillaris by preserving the endothelial PLVAP.