RETINAL DEGENERATION: A NEW ANIMAL MODEL

人类遗传性视网膜变性了解甚少

Human hereditary retinal degenerations are poorly understood diseases that begin in early, middle or late life and frequently procede to total blindness. Syndromes such as retinitis and age- related maculopathy are the most common disorders in the class of diseases. Experiments are proposed to elucidate the cause of blindness in an animal model for the human diseases. This model, the rd, or retinal degenerate strain of chickens, exhibits a recessive mode of genetic transmission of a defect that leads to blindness early in life. The lesion begins as a locus in the posterior fundus, spreads peripherally, has accompanying pigmentary changes and the visual cells die after electrophysiological tests show them defective. Therefore, this model is useful as a surrogate for studying human syndromes. Preliminary studies suggest that the defect causing blindness in rd chicks is at the level of visual transduction: the conversion of light energy to electrical impulse. Studies proposed in the current grant are aimed at examining several processes involved in visual transduction. Oxidative metabolism and visual pigment bleaching will be examined by the nitroblue tetrazolium histochemical reaction and the early receptor potential, respectively. Presence or absence of specific retinal proteins (such as visual pigment proteins and G-protein, will be examined by immunocytochemistry and protein separation techniques. We will determine if rhodopsin is phosphorylated in response to light and compare cylic nucleotide levels in the mutants to those in normally sighted chicks. Opsin synthesis and outersegment renewal will be examined biochemically and anatomically. Finally, the Na-K- ATPase molecule, which controls an important membrane ion pump in photoreceptors will be analyzed, as a possible cause/effect of the blindness. These experiments will provide insight into the cause of blindness and into the normal processes of visual transduction.