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 pathological 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 models of retinitis pigmentosa, light-induced lesions, histogenesis during development, and others. Apoptosis can be separated into several phases: the induction by a multitude of stimuli, the effector phase in which the apoptotic signal is transmitted to the cellular death machinery, the excecution period when proteolytic cascades are activated, and the phagocytic removal of cellular remnants. Control mechanisms for retinal apoptosis are only beginning to be clarified. Potential apoptotic 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 revealed an essential role of the immediate-early gene product c-Fos in light-induced apoptosis. c-Fos is a member of the AP-1 family of transcription 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 diurnal rhythm. Future studies will have to clarify how light can control the expression of specific genes, and specifically, the role of c-fos and other genes of retinal apoptosis including potential target genes and signaling pathways.