Melanin Aggregation and Polymerization: Possible Implications in Age-Related Macular Degeneration

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Abstract
The state of aggregation of the polymer melanin may determine its propensity to act either as an antioxidant or as a pro-oxidant. Age-related alterations in its state of aggregation are suggested to alter the degree of polymerization so as to confer increased pro-oxidant propensity to the melanin polymer. Degradative processes in/of melanosomes and lysosomes in the retinal pigment epithelium (RPE) appear to be intimately connected so that they may involve exchange of contents between these two organelles. An increased pro-oxidant environment inside lysosomes has been associated with preventing the digestion of cellular components including photoreceptor outer rod segments partly by altering function of lysosomal hydrolases. It is speculated that age-related accumulation of low-molecular-weight phototoxic pro-oxidant melanin oligomers within lysosomes in the RPE may be partly responsible for decreasing the digestive rate of incorporated cellular components (including photoreceptor outer rod segments) which may lead to lipofuscin formation. More work is required to definitively refute or support such a hypothesis.