Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

About the Mechanism of Light-Induced Age-Related Decrease of Melanin Concentration in the Retinal Pigment Epithelium Cells

Version 1 : Received: 24 July 2023 / Approved: 25 July 2023 / Online: 27 July 2023 (10:23:08 CEST)

A peer-reviewed article of this Preprint also exists.

Dontsov, A.E.; Yakovleva, M.A.; Vasin, A.A.; Gulin, A.A.; Aybush, A.V.; Nadtochenko, V.A.; Ostrovsky, M.A. Understanding the Mechanism of Light-Induced Age-Related Decrease in Melanin Concentration in Retinal Pigment Epithelium Cells. Int. J. Mol. Sci. 2023, 24, 13099. Dontsov, A.E.; Yakovleva, M.A.; Vasin, A.A.; Gulin, A.A.; Aybush, A.V.; Nadtochenko, V.A.; Ostrovsky, M.A. Understanding the Mechanism of Light-Induced Age-Related Decrease in Melanin Concentration in Retinal Pigment Epithelium Cells. Int. J. Mol. Sci. 2023, 24, 13099.

Abstract

It is known that during the process of aging there is a significant decrease in the number of melanosomes in the retinal pigment epithelium (RPE) cells of the human eye. We have previously shown that the interaction of melanin melanosomes with superoxide radicals results in its oxidative degradation with the formation of water-soluble fluorescent products. In the present study, we show using fluorescence analysis, HPLC, and mass spectrometry, that visible light irradiation of melanolipofuscin granules isolated from RPE cells of the human eye results in the formation of water-soluble fluorescent products of oxidative degradation of melanin, in contrast to lipofuscin granules and melanosomes irradiation. The formation of these products occurs as a result of oxidative degradation of melanin by superoxide radicals, which are generated by the lipofuscin part of the melanolipofuscin granule. We identified these products both in the composition of melanolipofuscin granules irradiated with visible light, and in composition of non-irradiated but oxidized by superoxide radicals, melanosomes. In melanolipofuscin granules irradiated with visible light, ions that could be associated to melanin oxidative degradation products were identified by applying principal component analysis of time-of-flight secondary ion mass spectrometry (ToF-SIMS) data. Degradation of the intact melanosomes by visible light is also possible; however, this requires significantly higher irradiation intensities than for melanolipofuscin granules. It is concluded that the decrease in the concentration of melanin in RPE cells of the human eye with age is due to its oxidative degradation by reactive oxygen species generated by lipofuscin as part of melanolipofuscin granules under the action of light.

Keywords

human eye; retinal pigment epithelium; melanosomes; melanolipofuscin granules; visible light; superoxide; melanin degradation

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

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