http://www.evrs.eu/medias/2005/congress/The-RPE-in-health-and-disease:-a-role-for-lipofuscin-and-melanin-in-ARMD.swf

Mike Boulton – School of Optometry and Vision Sciences, Cardiff University, Cardiff CF10 3NB, UK

The retinal pigment epithelium (RPE) is a single layer of post-mitotic cells, which functions both as a selective barrier to and a vegetative regulator of the overlying photoreceptor layer, thereby playing a key role in its maintenance. Through the expression and activity of specific proteins, it regulates the transport of nutrients and waste products to and from the retina, it contributes to outer segment renewal by ingesting and degrading the spent tips of photoreceptor outer segments, it protects the outer retina from excessive high-energy light and light-generated oxygen reactive species and maintains retinal homeostasis through the release of diffusible factors. The ageing characteristics of the RPE suggest that in addition to cell loss, pleomorphic changes and loss of intact melanin granules, significant metabolic changes occur resulting, at least in part, from the intracellular accumulation of lipofuscin. This pigment, which is strongly associated with geographic atrophy, is a potent photoinduciblegenerator of reactive oxygen species with the ability to damage proteins, lipids and nucleotides within the RPE culminating in cell dysfunction and death. In addition, remaining melanin granules within the aged RPE are no longer protective and instead act as an additional source of oxidative stress to the RPE. While the aetiology of agerelated macular degeneration is complex and is as yet unresolved, it is likely that agerelated changes in RPE pigments play a fundamental role in the development of this condition.