APOPTOTIC CELL-DEATH IN RETINAL DEGENERATIONS

Apoptosis is a regulated mode of single cell death that involves gene expression in many instances and occurs under physiological and pathol ogical conditions in a large variety of systems. We briefly summarize major features of apoptosis in general and describe the occurrence of apoptosis in the retina in different situations that comprise animal m odels of retinitis pigmentosa, light - induced lesions, histogenesis d uring development, and others. Apoptosis can be separated into several phases: the induction by a multitude of stimuli, the effector phase i n which the apoptotic signal is transmitted to the cellular death mach inery, the execution period when proteolytic cascades are activated, a nd the phagocytic removal of cellular remnants. Control mechanisms for retinal apoptosis are only beginning to be clarified. Potential apopt otic signal transducers were investigated in our laboratory, including metabolites of arachidonic acid and downstream mediators of signaling molecules such as transcription factors. Work in our laboratory revea led an essential role of the immediate-early gene product c-Fos in lig ht-induced apoptosis. c-Fos is a member of the AP-I family of transcri ption factors and, together with other members of this family, it may regulate apoptosis in the central nervous system. Expression of the c- fos gene in the retina can be evoked by light exposure and follows a d iurnal rhythm. Future studies will have to clarify how light can contr ol the expression of specific genes. and specifically, the role of c-f os and other genes of retinal apoptosis including potential target gen es and signaling pathways. (C) 1998 Published by Elsevier Science Ltd. All rights reserved.