Retinal cell apoptosis

Apoptosis in retinal cell populations has been detected in a wide range of eye diseases causing blindness. Compared to necrosis, apoptosis is an early maker of disease and represents a controlled form of cell death. It is now known that multiple pathways, including oxidative stress and nitric oxide synthase, and both mitochondrial-mediated caspase-dependent and -independent mechanisms are involved, with variations dependent on disease and cell type. The retina offers a compact and easily accessible route by which to examine these processes. The aim of this review is to appraise what is known about the apoptotic cell death pathways that are involved in important blinding retinal diseases, by considering results from animal models of retinal diseases and how they can relate to the human disease. Animal models have offered the opportunity to examine pathways of cell death in far greater detail than is possible in humans. Particular emphasis will be on the different intracellular mechanisms by which apoptosis leads to retinal neuronal death in animal models of retinal disease and whether this can be applied to the human disease, since understanding this is critical for developing therapies. These will encompass retinal dystrophies, age-related macular degeneration, glaucoma and diabetic retinopathy. Key challenges for treatment of retinal diseases will be targeting multiple pathways of apoptosis to effectively rescue cells and restore function.