Mechanisms of cell death in the inherited retinal degenerations

Abstract

The human retina possesses both extraordinary sensitivity and a huge adaptive range. A light flash containing only a few photons is sufficient to be consciously perceived in humans. We also can see over a range of nearly nine orders of magnitude in background illumination. The vertebrate visual system has been pushed, by evolutionary pressures, to approach its thermodynamic limitations. This exquisite tuning, however, comes at a cost. Photoreceptors are forced to carry large metabolic burdens, to renew continuously their light-sensitive outer segments and to exist under conditions of very high pO2. Modest changes in the biochemical environment or cellular structure of photoreceptors, caused by genetic lesions or environmental insults, are sufficient to induce cell death through apoptosis. For the inherited retinal degenerations, understanding the impact of each molecular defect on the biology of photoreceptors is important, in addition to studying how these effects converge upon the apoptotic pathway. Collectively, these studies should lead to the development of rational therapies that may slow or even reverse the progression of this devastating disease process.