We proposed that two aspects exert a combined action, which leads to a reduction of the level of VEGF-A in RP: on the one hand, a loss of RPE cells, which constitute an important source of VEGF in the eye
20 21 ; on the other hand, the relative retinal hyperoxia caused by photoreceptor degeneration.
22 Several in vivo studies have revealed that, in a normal eye, VEGF-A is produced constitutively by RPE cells,
20 21 whereas VEFG expression in the RPE is known to be essential for the development of choriocapillaris and visual function.
23 Retinal degeneration resulting from defects in genes normally expressed in photoreceptors also leads to the degeneration of the RPE.
24 The apoptosis of photoreceptors due to the different genetic mutations involved in RP
3 leads to RPE cell death, which may contribute to lower VEGF expression. Adult mice exposed to hyperoxia, which also increases oxygen in the retina, showed a decreased expression of VEGF in the retina. Furthermore,
rd mice, an animal model of RP, have been shown to display a decreased expression of VEGF in the retina. The investigators in that study believed that this was because photoreceptor cell death caused a decrease in oxygen usage and thinning of the retina, generating a relative hyperoxia in the inner retina, which, in turn, reduced VEGF expression by retinal cells such as pericytes, endothelial cells, glial cells,
25 Müller cells, and ganglion cells.
26 Of interest, another report demonstrated that neonatal mice with classic inherited retinal degeneration (
Pdeb rd1 /Pdeb rd1 ) failed to mount reactive retinal neovascularization in a mouse model of oxygen-induced proliferative retinopathy associated with an absence of the expected VEGF upregulation in the retina. The same study reported that a patient displayed spontaneous regression of retinal neovascularization, associated with long-standing diabetes mellitus, when RP became clinically evident. Both mouse and human data support the hypothesis that O
2 consumption by rod cells is a major driving force in ischemic retinal neovascularization and controls VEGF production.
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