Prevention of photoreceptor apoptosis by activation of the glucocorticoid receptor

PURPOSE. Evidence has accumulated that excessive light exposure may promote age-related and inherited retinal degeneration, in which photoreceptor dea th by apoptosis leads to loss of vision. In the current study, the effect o f elevated corticosteroid levels on light-induced apoptosis of photorecepto rs was determined. METHODS. Photoreceptor apoptosis was induced in retinas of BALB/c mice by e xposure to diffuse white light. High levels of corticosteroids were induced , either endogenously (fasting-mediated stress) or by a single intraperiton eal injection of dexamethasone (DEX). Photoreceptor damage was assessed mor phologically and by electroretinography. Glucocorticoid receptor (GR) and a ctivator protein (AP)-1 activities were shown by Western blot analysis and electrophoretic mobility shift assay (EMSA) of retinal nuclear extracts. RESULTS. Fasting and injection of DM led to an activation of GR in the reti na, as judged by its translocation to the nucleus of retinal cells. On indu ction of GR activity before light exposure, AP-1 activity, normally induced by damaging doses of light, remained at basal levels. Both treatments comp letely prevented photoreceptor apoptosis and preserved retinal function. CONCLUSIONS. Activity Of the transcription factor AP-1 is associated with l ight-induced apoptosis. In the current study, pharmacologic suppression of AP-1 activity protected against light damage. Inhibition of AP-1 activity m ay have occurred by the protein-protein interaction of GR and AP-1.