Everyday the light-sensitive cells in our retinas, the photoreceptors, shed and renew a portion of their light-sensitive membrane. Why this process occurs is not completely understood, however; it is ubiquitous to all animals studied to date. It is essential for proper visual function. In fact, retinal degeneration occurs in mutant rats unable to shed their photosensitive membrane. In most animals, shedding of the photosensitive membrane is regulated by a biological clock (circadian rhythm) and triggered by that clock and/or by light. Relatively little is known, however, about how the biological clock and light interact to trigger and regulate daily light-sensitive membrane shedding and renewal. The lateral eye of the horseshoe crab (Limulus) has long served as an important model system for the study of light-sensitive membrane shedding. Limulus provides the relatively unique advantage that, to date, there is no evidence of a biological clock in the eye; instead, circadian rhythms are communicated to the eye from a central clock in the brain along nerve fibers that run from the brain to the eye in the optic nerve. As a result, the effects of light and circadian rhythms on photoreceptor structure and function can easily be decoupled in this system. The investigator has developed a testable model for the interaction of light and the biological clock in the regulation of synchronous daily light-sensitive membrane shedding. The investigator proposes to evaluate this model through the following three specific aims. 1. Investigate the molecular pathways through which the biological clock prepares the retina for light-sensitive membrane shedding. 2. Determine whether the biological clock synchronizes light-sensitive membrane shedding via competitive enzymatic interactions. 3. Examine the role of the photoreceptor cell cytoskeleton in light-sensitive membrane shedding.
