Hyperoxia causes decreased expression of vascular endothelial growth factor and endothelial cell apoptosis in adult retina

Mice or humans with photoreceptor degenerations experience permeability and dropout of retinal capillaries. Loss of photoreceptors results in decrease d oxygen usage and thinning of the retina with increased oxygen delivery to the inner retina. To investigate the possibility that increased tissue oxy gen plays a role in the vascular damage, we exposed adult mice to hyperoxia , which also increases oxygen in the retina. After 1, 2, or 3 weeks of hype roxia, there was a statistically significant decrease in retinal vascular d ensity that was not reversible, and endothelial cell apoptosis was demonstr ated by TUNEL staining. Mice exposed to hyperoxia and mice with photorecept or degeneration both showed decreased expression of VEGF in the retina. Aft er complete or near-complete degeneration of photoreceptors, there was incr eased expression of VEGF in RPE cells, which may explain the association of photoreceptor degeneration and neovascularization in or around the RPE. In creased expression of VEGF in photoreceptors of transgenic mice failed to p revent hyperoxia-induced retinal capillary dropout. These data suggest that increased oxygen in the retina, either by increased inspired oxygen or by photoreceptor degeneration, results in endothelial cell death and dropout o f capillaries. Decreased expression of VEGF may be a contributing factor, b ut the situation may be more complicated for mature retinal vessels than it is for immature vessels, because VEGF replacement does not rescue mature r etinal vessels, suggesting that other factors may a Iso be involved. (C) 19 99 Wiley-Liss, Inc.