This project examines biochemical events unique to the retina, particularly the synthesis and modification of photoreceptor membrane components, in the retinas of vertebrates which can be affected by inherited retinal degenerations. The synthesis of the visual pigment, rhodopsin, occurs at a normal rate as measured by radioactive leucine incorporation following intravitreal injection in the eyes of miniature poodles affected with progressive rod-cone degeneration. Similarly, the glycosylation and acylation of rhodopsin were found to be normal following intravitreal injection of labeled fucose or palmitic acid, respectively. However, phospholipid synthesis or degradation, measured by radioactive palmitic acid incorporation, appears to be different in the affected dogs, suggesting a possible metabolic defect in this inherited disorder. The evidence suggests a significant diminution in the esterification of palmitic acid. Incubation of trephine punches of retina with labeled precursors produces the same labeling pattern in phospholipids as does intravitreal injection. Thus many precursors can be screened with a single retina. Transplacental exposure to the DNA alkylating reagent N-methyl-N- nitrosourea on day 16 of gestation in CD-l albino mice induces a progressive retinal degeneration beginning at 4-6 weeks of age. No obvious defect in either protein or phospholipid synthesis can be demonstrated. Thus a more subtle defect may have occurred such as the alteration of a small number of genes.
