Spreading mechanics and differentiation of astrocytes during retinal development

Abstract

The retinal vasculature supplies oxygen to the inner layers of the retina, the light-sensitive tissue in the eye. During development, formation of the retinal vasculature depends on prior establishment of a mesh of astrocytes, a type of glial cell, which guide the growth of the vascular network. Astrocytes emerge from the optic nerve head and proliferate and spread, forming a mesh-like layer over the retinal surface. The initially formed cells are termed astrocyte precursor cells (APCs), which differentiate into immature perinatal astrocytes (IPAs) during the prenatal period. A continuum model is developed to describe the proliferation, differentiation, and migration these cells. Effects of oxygen and growth factor levels on proliferation and differentiation are included. Cell migration is driven by gradients in tension in the astrocyte mesh, which varies inversely with total density. The resulting governing equations have the form of a nonlinear diffusion-like equation. The model can account for the observed radial spread over time of the astrocyte disk. Experimental observations show that the APCs form a narrow rim around the edge of this disk, with IPAs in the interior. The model predicts this behavior if the mobility of the APCs is assumed to be higher than that of the IPAs under a given tension gradient. Thus, the model shows how tension-driven cell motions can account for separation of cell types in a cell layer spreading over a substrate.