Circadian-dependent retinal light damage in rats

PURPOSE. TO determine the relative susceptibility of rats to retinal Light damage at different times of the day or night. METHODS. Rats maintained in a dim cyclic light or dark environment were exp osed to a single dose of intense green light beginning at various rimes. No rmally, Light exposures were for 8 or 3 hours, respectively, although longe r and shorter periods were also used. Some animals were treated with the sy nthetic antioxidant dimethylthiourea (DMTU) before or after the onset of li ght. The extent of visual cell loss was estimated from measurements of rhod opsin and retinal DNA levels 2 weeks after Light treatment. The time course of retinal DNA fragmentation, and the expression profiles of heme oxygenas e-1 (HO-1) and interphotoreceptor retinol binding protein (IRBP) were deter mined I to 2 days after exposure. RESULTS. When dark-adapted cyclic light-reared or dark-reared rats were exp osed to intense Light during normal nighttime hours (2000-0800) the loss of rhodopsin or photoreceptor cell DNA was approximately twofold greater than that found in rats exposed to light during the day (0800-2000). The relati ve degree of light damage susceptibility persisted in cyclic Light-reared r ats after dark adaptation for up to 3 additional days. For rats reared in a reversed light cycle, the light-induced loss of rhodopsin was also reverse d. Longer duration Light treatments revealed that dim cyclic light-reared r ats were three- to fourfold more susceptible to light damage at 0100 than a t 1700 and that dark-reared animals were approximately twofold more suscept ible. Intense light exposure at 0100 resulted in greater retinal DNA fragme ntation and the earlier appearance of apoptotic DNA ladders than at 1700. T he extent of retinal DNA damage also correlated with an induction of retina l HO-I mRNA and with a reduction in IRBP transcription. Antioxidant treatme nt with DMTU was effective in preventing retinal light damage when given be fore but not after the onset of Light. CONCLUSIONS. These results confirm earlier work showing greater retinal lig ht damage in rats exposed at night rather than during the day and extend th ose findings by demonstrating that a single, relatively short, intense Ligh t exposure causes a circadian-dependent, oxidatively induced loss of phoror eceptor cells. The light-induced loss of photoreceptor cells is preceded by DNA fragmentation and by alterations in the normal transcriptional events in the retina and within the photoreceptors. The expression profile of an i ntrinsic retinal factor(s) at the onset of light exposure appears to be imp ortant in determining light damage susceptibility.