TGF‐Beta is required for retinal vascular barrier function, endothelial cell survival and homeostasis of the adult retina

Cell‐cell interactions are critical to both vascular development and vessel stability in the adult and TGF‐β signaling between endothelial and underlying mural cells is a potent stabilization signal for the quiescent vasculature. Here we describe the effects of inhibition of TGF‐β signaling in the retinal vasculature by overexpressing soluble endoglin (sEng). TGF‐β inhibition increased vascular and neural cell apoptosis in the inner layers of the retina as determined by TUNEL staining, transmission electron microscopy and western blotting for cleaved caspase 3, concomitant with a decrease in inner retinal visual function as measured by electroretinogram (ERG). We further demonstrate impaired inner retinal vascular perfusion, retinal capillary collapse and an impaired ability to autoregulate peripheral blood flow in response to acetylcholine (ACh). Fundus angiography and evans blue permeability tests revealed increased circulating sEng causes breakdown of the blood‐retinal‐barrier due to a decrease in association of tight junction proteins zo‐1 and occludin. In vitro, inhibition of TGF‐β signaling leads to endothelial but not 10T1/2 cell death and dissociation of endothelial and 10T1/2 cells, concomitant with a breakdown of endothelial barrier function. Our results demonstrate a potent role for endogenous TGF‐β signaling in the quiescent retinal vasculature. Grant Funding Source NIH