Photoaging of human retinal pigment epithelium is accompanied by oxidative modifications of its eumelanin

Abstract

Although photodegradation of the retinal pigment epithelium (RPE) melanin may contribute to the etiology of age-related macular degeneration, the molecular mechanisms of this phenomenon and the structural changes of the modified melanin remain unknown. Recently, we found that the ratio of pyrrole-2,3,4,5-tetracarboxylic acid (PTeCA) to pyrrole-2,3,5-tricarboxylic acid (PTCA) is a marker for the heat-induced cross-linking of eumelanin. In this study, we examined UVA-induced changes in synthetic eumelanins to confirm the usefulness of the PTeCA/PTCA ratio as an indicator of photo-oxidation and compared changes in various melanin markers and their ratios in human melanocytes exposed to UVA, in isolated bovine RPE melanosomes exposed to strong blue light and in human RPE cells from donors of various ages. The results indicate that the PTeCA/PTCA ratio is a sensitive marker for the oxidation of eumelanin exposed to UVA or blue light and that eumelanin and pheomelanin in human RPE cells undergo extensive structural modifications due to the life-long exposure to blue light.

Mineralized rods and cones suggest colour vision in a 300 Myr-old fossil fish

“…To identify the presence of melanin in the fossil material, the alkaline hydrogen peroxide oxidation method [24][25][26][27] was used in the black to dark brown-coloured fossil eye fragments and the light brown-coloured rock matrix. Samples (8-17 mg) were ground to a fine powder using a mortar and pestle and added to water at a concentration of 10 mg per ml water and 100 ml aliquots were subjected to alkaline hydrogen peroxide oxidation 25 .…”

“…These molecules are common only to eumelanin and have never been produced by the alkaline hydrogen peroxide oxidation of any other biological material [24][25][26] . The PTeCA/PTCA ratio of 2.7 is extremely high as compared with those of extant fish retina (0.10 in Table 1) and bovine retinal pigment epithelium melanosomes (0.13), indicating extensive thermal modification of eumelanine 26,27 . The retinal area of A. bridgei has many mineralized rods, each about 2 mm wide and maximum length of about 18 mm (Fig.…”

Photoaging of retinal pigment epithelial melanosomes: The effect of photobleaching on morphology and reactivity of the pigment granules

“…There is also a loss of melanin and the remaining melanin granules exhibit substantially modified physicochemical properties that may reduce the antioxidant and photoprotective ability of RPE melanin and even enhance its phototoxic potential [3][4][5][6]. It has recently been demonstrated that RPE melanin from aged human donors exhibits substantial oxidative modifications and crosslinking, which might be aggravated by chronic exposure to shortwavelength visible light (402-508 nm) [7]. To study in vitro these age-related changes that in vivo occur over many years, we proposed a simple model of photoaging of RPE melanin, in which bovine or porcine RPE melanosomes were exposed to intense visible light to induce different degree of their photobleaching [8][9][10].…”

The Ultrastructure, Spatial Distribution, and Osmium Tetroxide Binding of Lipofuscin and Melanosomes in Aging Monkey Retinal Epithelium

“…15 Melanosomes may be lost by extrusion through the basal membrane of the epithelium into Bruch’s membrane, where they might be dissolved by macrophages. Melanosomes are also subject to photo-toxicity 16 which can be modulated by lipofuscin. 17 …”