INTRARETINAL OXYGEN DISTRIBUTION IN URETHANE-INDUCED RETINOPATHY IN RATS

This study was performed to explore the interaction between chronic ne ural degeneration and the subsequent vascular remodeling. Weekly ureth an administration in rats from birth produces a retinopathy model char acterized by photoreceptor degeneration, retinal vascular regression, and retinal pigment epithelium (RPE) neovascularization. We investigat ed the hypothesis that altered oxygen distribution across the retina a nd choroid could be involved in the vascular changes seen in this reti nopathy. We compared measurements of vitreal, intraretinal, and choroi dal oxygen tension (Po-2) distribution in anesthetized and ventilated control and urethan-treated rats at 8 and 16 wk of age with the use of oxygen-sensitive microelectrodes. Striking differences were observed in both choroidal and intraretinal Pot distribution in urethan-treated rats compared with controls. At both ages, intrachoroidal Po-2 was mu ch lower in the urethan-treated rats. In addition, the intraretinal Po -2 distribution across the inner retinal layers was more uniform than normal. A small elevation in Po-2, was present at 8 wk in the inner nu clear layer where subsequent vascular regression occurred, and a small reduction in Po-2 was present at the RPE, which recovered to normal v alues by 16 wk in regions where RPE vessel networks were first evident . Although. the retinal arteries were considerably thinner at both age s in the urethan-treated rats, the vitreal Po-2 profiles and superfici al retinal Po-2 remained normal. The unexpected and large reduction in the oxygen delivery from the choroid found in the urethan-treated rat s may account for the lack of major hyperoxia within the pathological retina and the lower oxygen tension in the RPE before the vascular pro liferation in this region. We propose that tissue Po-2 is an important determinant of the vascular remodeling, which is seen in this model o f neural degeneration and that the Po-2 distribution changes described in this study help provide a new view of the pathogenesis of this mod el.