Balance of oxygen supplies between retinal and choroidal circulations under hypoxia. (a) Under systemic hypoxia, the retinal circulation provides more oxygen to the outer retina to compensate the deficit from the choroidal circulation. (b) Anatomical structure of a rat retina. The retinal pigment epithelium (RPE) resides beneath the neural retina, which consists of several defined layers: the outer (OS) and inner segment (IS) of the photoreceptor, and the outer nuclear layer (ONL), outer plexiform layer (OPL), inner nuclear layer (INL), inner plexiform layer (IPL), ganglion cell (GC), and nerve fiber layer (NFL). The boundary between the inner retina and outer retina is the OPL. (c) Simulated PO2 profile across the retina (Supplementary Fig. S9). The inner retinal PO2 is assumed to be constant under the level of hypoxia used here, while the outer retinal PO2 profile changes. The majority of the oxygen is consumed in the IS, where the PO2 reaches a minimum in the outer retina. The oxygen diffuses from both the choroidal and retinal circulations, forming two PO2 gradients toward the IS. This distinct PO2 profile in three segments in the outer retina can be modeled by a one-dimensional oxygen diffusion model. (d) Comparison of the oxygen metabolism from experimental observation and simulation. The experimental oxygen metabolic rate is re-plotted from Figure 4i.