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Malgorzata B. Rozanowska, Ruth Edge, Jonathan Hawkett; Age-related Changes in Human RPE Melanosomes Lead to Loss of their Antioxidant Action and Enhanced Pro-oxidant Action in Oxidation Catalysed by Iron. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3362.
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To determine the effect of aging on interaction of retinal pigment epithelium (RPE) and choroidal melanosomes with iron ions and iron-mediated oxidation.
Melanosomes were isolated from human RPE and choroid from donor eyes pooled into three age groups: <47 (YMs), 60-75 (MMs) and >80 (OMs) years old. A part of YMs was pre-exposed to visible light. Oxidation of melanosomes with and without exogenous unsaturated lipids was induced by Fe-ADP in the presence or absence of ascorbate or NADPH+H2O2 in dark or during exposure to visible light. Concentration of melanin free radicals and melanin-bound Fe(III) was determined by electron spin resonance (ESR) spectrometry. Oxidation was monitored by ESR oximetry and generation of hydroxyl radicals - by ESR spin trapping.
In dark, YMs inhibited effectively in a dose-dependent manner both: Fe-catalysed oxidation of lipids and generation of hydroxyl radicals due to decomposition of hydrogen peroxide. Oxidations in the presence of MMs and OMs were significantly faster than for YMs. Illumination with visible light of YMs in the presence of iron led to ~3-fold slower oxidation than for older melanosomes. Photodegradation of YMs led to a partial loss of their antioxidant properties, and enhanced pro-oxidant action, similar to old melanosomes.
Interactions of melanosomes with iron ions change during ageing resulting in a loss of their protective properties against Fe-catalysed oxidation and generation of hydroxyl radical. Moreover, with ageing the ability of melanosomes to mediate redox-cycling of Fe ions becomes enhanced resulting in their pro-oxidant action. Considering that with aging there is accumulation of Fe ions in the RPE and choroid, and it is further increased in AMD, it can be suggested that age-related changes in interactions between melanosomes and iron can contribute to oxidative stress in the aged retina and development of AMD.
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