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Age-Related Macular Degeneration: Understanding the Roles of Lipofuscin, Macular Carotenoids and Reactive Oxygen Species L. Mulroy*, D.J. McGarvey*, T.G. Truscott*, M. Bolton^ and S.Davies^ * Chemistry Department, Keele University, Staffs, ST5 5BG, England ^ Department of Opthalmology, University of Manchester, Manchester, M13 9WH, England INTRODUCTION Age-related macular degeneration (ARMD) is the most dominant cause of blindness in the developed world for people over the age of 60. To date there is no medical treatment or preventative medicine against ARMD. There are several factors thought to be involved in the development of this disease but these are not yet fully understood or proven. The main theories implicate sunlight, age-related build-up of lipofuscin in the eye, genetic and nutritional factors as well as a reduction in antioxidant activity due to the ageing process as contributing factors in accumulated damage to the eye. This project involves an investigation of the possible roles of lipofuscin, reactive oxygen species and the macular carotenoids in retinal phototoxicity and protection. Lipofuscin is a granular material that accumulates with age in a variety of organ tissues including the retinal pigment epithelium (RPE) within the eye. The presence of lipofuscin is associated with many age-related and pathological conditions including: cirrhosis of the liver, cardiac hypertrophy and ARMD. The composition, formation and role of lipofuscin in the development of age-related diseases are not well understood. Studies of retinal lipofuscin have demonstrated that it can generate reactive oxygen species following light excitation indicating a potential role for lipofuscin in ARMD. The human retina contains the carotenoids lutein and zeaxanthin which are concentrated in the fovea region Carotenoids, generally, are known for their antioxidant ability and have the potential to quench damaging radicals and excited states. The macular carotenoids may therefore offer photoprotection to the retina by attenuating potentially damaging blue light and by acting as antioxidants via free radical scavenging. PROJECT OBJECTIVES To establish the mechanisms underlying macular degeneration and to explore potential preventative measures based on dietary antioxidants such as carotenoids (present in many fresh fruits and vegetables), vitamin E (present in oils) and vitamin C (found in many citrus fruits). To identify any phototoxic or protective effects of lipofuscin and carotenoids on RPE cell behaviour and then clarify their roles in these effects. To assess lipofuscin for its effect on enzyme activity and its ability to induce the peroxidation of lipids. To determine the photochemical properties of retinal lipofuscin and the macular carotenoids. To establish the mechanisms of retina photoprotection by macular carotenoids by investigation of excited state and free radical quenching.