ABERRANT EXPRESSION OF C-FOS ACCOMPANIES PHOTORECEPTOR CELL-DEATH IN THE RD MOUSE

Selective degeneration of rod photoreceptor cells in the retinal degen erative (rd) mouse prior to their complete maturation is thought to re sult from elevated cyclic guanosine monophosphate (cGMP) levels owing to the inherited defect in cGMP-phosphodiesterase. To investigate pote ntial signaling pathways which might lead to apoptotic death of photor eceptors in the rd retina, the expression of immediate-early genes (IE G) of the activating protein-1 transcription factor (AP-1) family was examined, increasing numbers of apoptotic photoreceptor nuclei were ob served in the outer nuclear layer of the rd mouse beginning at postnat al day (P) 10, The peak incidence of apoptotic cells was observed at P 13; by P16, almost the entire population of photoreceptors had been lo st. Although c-Fos-like immunoreactivity was absent in photoreceptors of normal retinas, we observed that commencing at around P10, increasi ng numbers of rod photoreceptors in the rd retina exhibited nuclear st aining for c-Fos protein, While no change in the distribution patterns of other members of the AP-1 family (c-Jun, JunB, and JunD) was obser ved in photoreceptors, Muller cell nuclei were transiently immunoreact ive for c-Jun on P11, The incidence of c-Fos-positive photoreceptors p eaked sharply at P12, 1 day earlier than the peak in apoptosis, Furthe rmore, the population of c-Fos-positive photoreceptors was distinct fr om apoptotic photoreceptors exhibiting chromatin condensation, The abe rrant expression of c-Fos protein in rod photoreceptors immediately pr ior to their death in the rd mouse raises the possibility that c-Fos m ay be directly or indirectly involved in triggering the apoptotic casc ade. Furthermore, the additional finding of c-Jun induction in Muller glia suggests that the IEG response to photoreceptor degeneration invo lves both intra- and intercellular signal transduction pathways, (C) 1 997 John Wiley & Sons, Inc.