Macular Degeneration is Often Associated with Retinal Lipofuscinosis

neous mixture of both proteins and lipids that are partially oxidized (67). It is thought that lipofuscin accumulation is a major causal factor in AMD because it correlates with the severity of photoreceptor degeneration (94) and has been shown to have toxic properties (21, 68). The major fluorescent component of lipofuscin is Nretinylidene-N-retinylethanolamine (A2E), which is a metabolite of retinal, visual pigment. A2E has been shown to perturb lysosomal function (21, 68), disrupt membrane integrity by a detergent-like effect (19), and promote programmed cell death (70). Proteomic analysis shows that various components of lipofuscin are derived both from photoreceptors and RPE (67). A possible explanation of this dual cellular origin is provided by the fact that photoreceptor outer segments are renewed by the daily phagocytosis of the tips of photoreceptors by RPE cells (5, 54). It would therefore make sense if lipofuscin accumulation were related to a problem of phagocytosis or lysophagosome function (18). In any case, lipofuscin seems to be a noxious material. Lipofuscin accumulation is also associated with a group of neurodegenerative diseases called neuronal ceroid lipofuscinoses (NCLs). NCLs are lysosomal storage diseases characterized by accumulation of lipofuscin pigment, blindness due to retinal degeneration, psychomotor retardation, and premature death (15, 27, Your ability to read this article without magnification requires the normal functioning of your macula. The macula is a small region near the center of the retina responsible for high-acuity vision due to its high density of cone photoreceptors. Almost everyone knows somebody, often a parent or grandparent, who has the progressive disorder known as macular degeneration. When it occurs beyond the 5th decade of life and has no specific diagnosis, it is called “age-related macular degeneration” (AMD). AMD is the leading cause of blindness in technologically developed countries (57). (World wide, cataracts, trachoma, and glaucoma rank higher.) AMD has been estimated to affect ~20% of the population over the age of 65 and >35% of individuals over the age of 75 (73).