Circadian effects on retinal light damage

Abstract

Light-induced retinal damage has long served as a model of retinal dysfunction and visual cell loss arising from inherited disease or caused by oxidative stress. Its utility resides in the fact that nearly the entire complement of retinal photoreceptors is simultaneously involved in a now well-defined progression of cellular degeneration and active cell death. Numerous extrinsic factors are known to infl uence the extent of visual cell loss, including previous light-rearing history, light intensity and duration, and diet. However, visual cell damage is also impacted by intrinsic factors such as circadian rhythms. These endogenous rhythms are known to affect the cellular machinery involved with light reception and metabolism, receptor function and signaling, and the cascade of apoptotic cell death. Herein we describe the progression of light-induced oxidative damage and visual cell death in retina and how circadian-dependent gene expression affects the process. The time course of retinal gene expression and light damage susceptibility has been compared at various times of the day or night. In addition to genes known to exhibit a circadian profile of regulation, we also describe a number of genes previously not recognized as affecting the progression of visual cell damage and loss.