Abstract
Abstract: :
Purpose: The retinal vasculature is attenuated in humans with retinitis pigmentosa (RP) and in animal models of photoreceptor degeneration. Here we assessed whether retinal vessels at different stages of degeneration still respond to changes in blood oxygen, and how vessel properties were correlated with histological measurements of retinal thickness. Methods: Eight Abyssinian cats (1 to 6.5 years old) with stages 1 (early) to 4 (late) of a slow hereditary photoreceptor degeneration were used. Color fundus photographs were taken of the retinas during acute experiments while the animals were breathing air, 100% oxygen, and 10% oxygen. Measurements of vessel diameter were made from selected points on digitized photographs. At the end of the experiments, the retinas were fixed in 2% glutaraldehyde in 0.1 M cacodylate buffer. They were then processed and stained with toluidine blue for light microscopy (and electron microscopy). Measurements were made of total and outer retinal thickness (at 400X) as well as photoreceptor nuclei per section (at 1000X) in the area centralis and far periphery. Results: Diameters of retinal vessels decreased as the disease progressed, with stage 1 animals being indistinguishable from normal cats, and a stage 4 cat having vessels that were barely detectable. In all animals, hypoxemia caused an increase in the diameter of arteries and veins. Hyperoxia decreased vessel diameters in most animals. Photoreceptor counts were well correlated with total retinal thickness and outer retinal thickness across animals and stages of the disease. Decreases in photoreceptor numbers in the area centralis did not occur until late in the disease process (stage 4). The decrease in the periphery occurred earlier (stage 3). The thickness of the inner retina was well-preserved during the entire course of photoreceptor degeneration. Conclusions: Retinal vessels become severely attenuated late in photoreceptor degeneration, but regulate normally in response to oxygen. Despite the attenuation, the combination of choroidal and retinal circulations retains the ability to nourish the inner retina. Taken together with our earlier work, these results show that changes in vessels precede the structural loss of photoreceptors, and are more closely related to the loss of photoreceptor function.
Keywords: retinal degenerations: hereditary • retinitis • blood supply