Experimental evidences indicate that many aspects of mammalian retinal physiology and function are under the control of a retinal circadian clock. Studies also indicate the retinal molecular clock and its output signals contribute to retinal disease and pathology. Bmal1 is a key component of the circadian molecular circadian clock mechanism. Our previous studies indicate that the removal of Bmal1 from retina modulates neural circuitry of retina and cone photoreceptors viability. The goal of the present proposal is to investigate the role of retinal circadian clock in retinal function and SCN circadian organization. The present application comprises three specific aims. In specific aim 1, we will investigate the mechanism underlying clock regulation of cone viability using 661W cell line. In specific aim 2, we determine whether the environmental circadian disruption (ECD, e.g. jet lag) affects retinal function and circuitry. In specific aim 3, we will test the hypothesis that the removal of Bmal1 from retina alters circadian behavior rhythm. In our research, we will use a wide array of new and technologically advanced techniques as well as several lines of transgenic mice and cell line will be used. Our proposal will provide important insights into the role of circadian clock in the modulation of visual function, photoreceptors viability and behavior rhythm.

The widespread control of signaling, metabolism, and gene expression exerted by the retinal circadian clock which contributes to many types of retinal diseases. The experiments proposed in our application will elucidate the role of retinal clock in cell viability, neural circuitry and behavior rhythm.