Modeling human retinal vascular pattern around foveal avascular zone.

Abstract Human retinas have unique anatomical structures called the macula and an associated characteristic vascular pattern. Despite its clinical importance, the mechanism of the unique vascular pattern formation in humans remains unknown because there are limitations in experimental approaches using primate samples. In this study, we developed a mathematical model of human retinal vascular development by considering endothelial cells and astrocytes. We assumed that retinal vessels are formed in angiogenesis according to the gradient of vascular endothelial growth factor (VEGF) and that astrocytes dynamically expand while avoiding the fovea, providing scaffolds for angiogenesis. Our model recapitulated various features of human retinal vascular pattern such as a radially outward vascular pattern from the optic disc, inferior and superior temporal arcades, foveal avascular zone (FAZ) formation, a radially inward vascular pattern around FAZ, and vertically facing pattern toward the horizontal vascular raphe. These results also suggest the importance of astrocyte dynamics in human retinal vascular pattern formation. Our modeling framework can be extended to abnormal vascular patterns observed in diseases, including retinopathy of prematurity.