Factors Underlying Circadian Dependent Susceptibility to Light Induced Retinal Damage.

Retinal cell loss in diseases such as Retinitis Pigmentosa occurs through an apoptotic process.1 The mechanism of this cell loss is not completely understood. Models that allow for the study of conditions in which the retina is susceptible or resistant to retinal damage help to elucidate the mechanism underlying the cell death. One model that is used to study retinal cell loss is the light induced retinal degeneration (LIRD) model.2 Intense light exposure leads to rhodopsin bleaching2 and is the trigger for the subsequent photoreceptor cell degeneration, as blocking the regeneration of rhodopsin prevents photoreceptor cell death.3 Oxidative stress is also involved in retinal degeneration,2,4-7 and the administration of natural or synthetic antioxidants prior to light exposure prevents the subsequent cell loss.7-13 Many factors can influence the extent of light induced damage including prior light history of the animals, age, genetics, and diet.4,8,14 The extent of LIRD is also dependent on the time of light exposure initiation. Animals exposed to light during the dark phase of the dark-light cycle suffer greater retinal damage than rats exposed to light during the day.15 More recently, it was reported by Organisciak et al that relatively brief intense light exposure commencing at 0100h lead to a 2-4 fold greater loss of photoreceptor cells in rat retina than light exposure beginning at 1700h.16 A fundamental question then is to ask what differences exist in the retina at various times of the day. It was suggested that endogenous factors regulated in a circadian manner might be involved in the observed difference in susceptibility to LIRD.16 Circadian rhythms cue an organism about night/day changes, have a period of approximately 24 hours, and persist in constant darkness or constant light. These rhythms are entrained by light, but can also be entrained by temperature17 and feeding.18 Circadian rhythms underlie many physiological processes that can lead to a stress tolerant or susceptible environment. There are several prominent circadian regulated physiological processes in the retina. Melatonin and dopamine are synthesized in a circadian manner or in response to light-dark cues, and may be involved in entraining the circadian cycle. They are the most obvious candidates for involvement in increased retinal susceptibility to light. Phototransduction protein levels are also important candidates as they are directly involved in modulating the retinas response to light. A fairly new candidate is metabolic activity of the retina. Increased metabolic activity results in decreased pH levels which may also play a key role as it has been shown to be involved in inducing apoptosis.19 Any or all of these factors may be involved in the circadian dependent susceptibility to light damage. [ABSTRACT FROM AUTHOR]