Figure 1.

Location of the inner-Blood-Retinal-Barrier (iBRB) and retinal endothelial cells. The neural retina comprises several distinct layers. In the orientation of this diagram, light enters from the top and passes through the retinal layers to reach rod and cone opsins in the outer segments (OS) of photoreceptors. Photoreceptor nuclei form the Outer Nuclear Layer (ONL). Photoreceptor cells form synaptic connections with downstream inter-neurons in the Outer Plexiform Layer (OPL). Nuclei of Bipolar Cells, Horizontal Cells, and some Amacrine Cells comprise the Inner Nuclear Layer (INL). In the Inner Plexiform Layer, the Bipolar and Amacrine Cells form synaptic contacts with Ganglion Cells in the Ganglion Cell Layer (GCL). An Inner-Limiting Membrane (ILM) lays on top of the retina and the superficial plexus. Two different blood supplies support the neural retina and both have a high-barrier character, which are collectively the Blood-Retinal-Barrier (BRB). The outer-BRB (oBRB) sustains photoreceptor cells and Retinal Pigment Epithelial (RPE) cells and is formed by the fenestrated choroidal vasculature, Bruch’s membrane and the RPE. The RPE cells, not the choroidal endothelial cells, provide the high-barrier nature of the outer-BRB. The inner-BRB (iBRB) sustains neurons of the inner retina and comprises three microvascular beds, the superficial, intermediate, and deep plexus (shown by red tracts). These are collectively referred to as the neural retinal vasculature. The endothelial cells of the neural retinal vasculature are responsible for the high-barrier nature of the iBRB.