Preliminary investigations of dopamine (DA) metabolism by the applicant showed that there is a large reduction in DA synthesis and release in rds, compared to normal, mice. Because DA has been shown to act as a neuromodulator of circadian and adaptive phenomena in the retina, the applicant postulates that abnormalities in DA metabolism may affect photoreceptor viability in genetic retinal degenerations. Homozygous and heterozygous rds mice, as well as normal mice, will be used. The first specific aim will determine the diurnal pattern of DA metabolism throughout the progression of retinal degeneration using HPLC.
The second aim will determine DA-dependent cAMP metabolism in mutant photoreceptors. Finally, the fourth aim will determine the consequences of DA depletion in normal retinas on photoreceptor viability, cAMP metabolism and diurnal disc shedding.
