The long range objectives of this proposal are to understand the following aspects of vertebrate retinal photoreceptor renewal: 1) Why do the light-sensitive disk membranes in photoreceptor outer segments need to be replaced at such a rapid rate and metabolic expense? 2) What regulates the balance between new disk synthesis an old disk shedding to maintain rod photoreceptors in a homeostatic state? 3) Are deficiencies in the processes of disk assembly or shedding responsible for photoreceptor pathological states such as those found in phototoxic responses, retinal detachment or nutritional deficiencies? Specific aims of the study are to use light microscope methods in conjunction with immunohistochemistry and spectroscopy to investigate the following: 1) What role does lipid peroxidation play in structural and functional changes found in rod cell disk membranes as they get older? 2) Do cytoskeletal elements and circadian chemical changes (melatonin) control disk membrane synethesis? 3) Are cytoskeletal elements or proximity of distal disks with the pigment epithelium relevant cues for triggering disk shedding? 4) What effects do photosensitizing drugs, nutritional deficiencies and retinal detachment have on disk assembly and axial displacement as measured by optical inhomogeneities (light-dark cycle dependent transaxial birefringence bands, membrane refractive index bands) or by axial movement of dye-labeled disk membranes? 5) Does the donor age have any observable effect upon human photoreceptor optical properties?
