Autophagy is One of the Multiple Mechanisms Active in Photoreceptor Degeneration

Abstract

Photoreceptor degeneration in human photoreceptor dystrophies and in the relevant animal models has been thought to be executed by one common mechanism – caspase-mediated apoptosis. However, recent experiments have challenged this concept. Gene defects or environmental stressors appear to cause oxidative stress and altered metabolism, which appear to induce caspase-dependent and caspase-independent cell death mechanisms such as the activation of cysteine-proteases, lysosomal proteases and autophagy and possibly complement-mediated lysis. In this article, we point out mechanistic parallels between these pathways and summarize our recently published investigation using a temporal analysis of the different pathways, which suggests that the non-caspase-dependent mechanisms may actively participate in the demise of the photoreceptors rather than represent a passive response of the retina to the presence of dying cells. Our investigation revealed that unless the common upstream initiator for a given photoreceptor dystrophy can be found, multiple rescue paradigms need to be used to target all active pathways.Addendum to:Multiple, Parallel Cellular Suicide Mechanisms Participate in Photoreceptor Cell DeathH.R. Lohr, K. Kuntchithapautham, A.K. Sharma and B. RohrerExp Eye Res 2006; 83:380-9