LIGHT HISTORY AND AGE-RELATED-CHANGES IN RETINAL LIGHT DAMAGE

PURPOSE. To determine the effects of age and long-term light-or dark-r earing environments on acute, intense-light-mediated retinal degenerat ion. METHODS. Male albino rats were maintained in a dim cyclic light e nvironment or in darkness for as long as 1 year. When aged 2, 4, 8, an d 12 months, some rats were given the synthetic antioxidant dimethylth iourea (DMTU) by intraperitoneal injection and were exposed to intense visible light for as long as 24 hours. Uninjected control rats were e xposed to light at the same time. Other rats were treated with light O f lower intensity for various periods. Two weeks after intense-light t reatment, photoreceptor cell degeneration was estimated by determining the level of rhodopsin and by measuring the content of photoreceptor cell DNA. Light-induced changes in retinal DNA were analyzed immediate ly after exposure by neutral gel electrophoresis and by 8-hydroxy-deox yguanosine measurements. Expression of the antioxidative stress protei n heme oxygenase-1 (HO-1) was determined by not-them blot analysis of mRNA in retinal extracts. RESULTS. At all ages, rats reared in cyclic dim-light conditions had lower rhodopsin levels than did rats reared i n darkness; photoreceptor cell DNA levels were unaffected by the reari ng environment. Senescent losses in rhodopsin and retinal DNA were sig nificant after rats were 12 months old. Dim-light-reared rats exhibite d an age-related increase in retinal light damage susceptibility, wher eas dark-reared rats were equally susceptible to damage at all ages. I n both types of rats, the mechanism of light-induced cell death involv ed an apoptotic process, visualized by the pattern of DNA fragments on electrophoretic gels. The process also induced the expression of HO-1 mRNA. Photoreceptor cell loss determined by biochemical measurement, DNA fragmentation, and HO-1 induction were dramatically reduced by the administration of DMTU. CONCLUSIONS. The age-related increase in susc eptibility to retinal light damage in rats is influenced by their long -term daily light history. Decreasing retinal irradiance by dark-reari ng eliminates the age-related increase in light damage, suggesting a c orrelation between light environment and retinal gene expression assoc iated with damage. In all rats, retinal light damage resulted in a pat tern of DNA. fragmentation consistent with apoptotic cell death and in an increased expression of HO-1 mRNA. Antioxidant treatment greatly r educed apoptosis and HO-1 expression. This indicates that light damage involves an oxidative process that may also trigger apoptosis in the retina. The sat aging model may provide useful insights into the role of light environment associated with retinal degeneration in an aging human population.