March 2012
Volume 53, Issue 14
ARVO Annual Meeting Abstract  |   March 2012
Pro-oxidant Properties of Human Retinal Melanolipofuscin in the Presence of Iron Ions; Comparison with Lipofuscin and Melanosomes
Author Affiliations & Notes
  • Malgorzata B. Rozanowska
    Optom & Vis Science, Cardiff University, Cardiff, United Kingdom
  • Ruth Edge
    University of Manchester, Manchester, United Kingdom
  • Floriana Tuna
    EPSRC National Service for EPR Spectroscopy,
    University of Manchester, Manchester, United Kingdom
  • Footnotes
    Commercial Relationships  Malgorzata B. Rozanowska, None; Ruth Edge, None; Floriana Tuna, None
  • Footnotes
    Support  The EPSRC UK National Electron Paramagnetic Resonance Service at the University of Manchester
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 6467. doi:
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      Malgorzata B. Rozanowska, Ruth Edge, Floriana Tuna; Pro-oxidant Properties of Human Retinal Melanolipofuscin in the Presence of Iron Ions; Comparison with Lipofuscin and Melanosomes. Invest. Ophthalmol. Vis. Sci. 2012;53(14):6467.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: : Both melanolipofuscin (MLF) and iron accumulate with age in the human retinal pigment epithelium (RPE). Accumulation of iron is further increased in age-related macular degeneration (AMD). The purpose of this study was to investigate interactions between iron and MLF as a source of oxidative stress and compare it with melanosomes (MS) and lipofuscin (LF).

Methods: : MLF, MS and LF granules were isolated from human RPE from cadaver eyes above 60 years old. Concentration of melanin radicals and melanin-bound Fe(III) was determined by electron spin resonance (ESR) spectrometry. Pigment granules with and without exogenous unsaturated lipids were exposed to Fe-ADP in the presence or absence of electron donors (ascorbate or NADPH) and/or hydrogen peroxide in dark or during exposure to visible light. Oxidation was monitored by ESR oximetry and generation of hydroxyl radicals - by ESR spin trapping.

Results: : Incubation of MLF in the presence of 0.05 mM Fe-ADP resulted in oxygen uptake which rate was over 3 and 7-fold greater than for MS and LF, respectively. During concomitant exposure to ascorbate or visible light, the rate of oxidation in suspension of MLF increased by a factor of ~2 and ~6, respectively. When MLF was irradiated in the presence of both Fe-ADP and ascorbate the rate of oxygen uptake was further increased and was ~5.8 times greater than for samples incubated in dark. MLF effectively inhibited Fe-catalysed formation of hydroxyl radicals from decomposition of hydrogen peroxide but was less efficacious than MS in inhibiting Fe-catalysed lipid peroxidation. During exposure to light, MLF was a substantial source of hydroxyl radicals and this effect was exacerbated in the presence of Fe ions.

Conclusions: : In the presence of iron ions melanolipofuscin is more reactive that melanosomes and lipofuscin. Reactivity of melanolipofuscin is further exacerbated in the presence of physiological reductants and by exposure to visible light. Melanolipofuscin in the aged retina with weakly chelated iron ions provides a greater source of oxidative stress than melanosomes or lipofuscin granules. This effect is further exacerbated during exposure to visible light. Therefore, melanolipofuscin is likely to play a significant role in the development and progression of AMD.

Keywords: retinal pigment epithelium • oxidation/oxidative or free radical damage • radiation damage: light/UV 

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