Recruitment of pericytes and astrocytes is closely related to the formation of tight junction in developing retinal vessels

Abstract

During retinal development, retinal vascularization begins in the inner retinal layer and sprouts radially from the optic nerve to reach the periphery of the retina. Subsequently, retinal vessels sprout into the deep retinal layer to form three parallel of the nerve fiber layer and two plexiform layers. In this process, endothelial cells are closely related to astrocytes and pericytes with strict chronological order. Here, we provide that the recruitment of pericytes and astrocytes to vascular tube of endothelial cells is closely associated with the formation of tight junction in developing retinal vessels. At P4, endothelial cells of retinal vessels behind the invading front directly contact to pericytes, but not to foot processes of astrocytes, where ZO-1 was already weakly immunoreactive along retinal endothelial cells. With the progression of retinal development, foot processes of astrocytes are gathered around retinal vessels and the maturation of tight junction in endothelial cells is clearly defined, which was temporally and spatially accordant to the expression of a tight junction protein, ZO-1. In addition, tight junction could be formed with contact of pericytes to endothelial cells without the prominent ensheathment of astrocytic foot processes, which coincided with the appearance of a tight junction protein, ZO-1. Therefore, these data demonstrate that the tight junction of endothelial cells in the blood-retina barrier could be developed by cellular interactions between pericytes, astrocytes, and endothelial cells. Moreover, ZO-1 as well as occludin or claudin might demonstrate the tightness of blood-retina barrier in developing retina.