Cell death in age-related macular degeneration

The cellular and molecular mechanisms underlying the death of photoreceptor s and other retinal cells in age-related macular degeneration (AMD) remain poorly understood. Some of the questions for which answers need to be sough t, and which are explicitly or implicitly addressed in this article include : (1) how do patterns of cell death in AMD compare, qualitatively and quant itatively, with "normal" cell death in aging retinas, and with cell death i n retinitis pigmentosa (RP) and its animal models; (2) is apoptosis involve d in AMD; (3) is there any evidence that rods are necessary for cone surviv al; (4) if the answer is yes, is there evidence that rods produce one or mo re survival-promoting factor(s) that act directly on cones; (5) are the eff ects of rods upon cones exclusively mediated by diffusible factors, or do t hey also involve contact-mediated interactions; (6) is there any evidence t hat photoreceptors regulate the survival and/or function of RPE and Muller cells, as well as the interactions between these cells and cones; (7) are t rophic factors and their receptors in the macula different from those in ot her parts of the retina; and (8) are toxic mechanisms involved in the onset and progression of cell death in AMD? Clear cut answers to most of these ( and related) questions about cell death in AMD are not yet available. The g oal of this article is to summarize discussion that should help in the form ulation of suitable hypotheses, amenable to experimental analysis. To provi de a platform for such discussion, we present an overview of progress made in recent years in the analysis of other retinal degenerations and of neuro nal degenerations in other regions of the CNS. We conclude with an overview of concepts and speculation derived from our current research.