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Review
. 2024 Mar 23;25(7):3609.
doi: 10.3390/ijms25073609.

Retinal Pigment Epithelium Pigment Granules: Norms, Age Relations and Pathology

Alexander Dontsov  1 , Mikhail Ostrovsky  1
Affiliations
Review

Retinal Pigment Epithelium Pigment Granules: Norms, Age Relations and Pathology

Alexander Dontsov et al. Int J Mol Sci. .

Abstract

The retinal pigment epithelium (RPE), which ensures the normal functioning of the neural retina, is a pigmented single-cell layer that separates the retina from the Bruch's membrane and the choroid. There are three main types of pigment granules in the RPE cells of the human eye: lipofuscin granules (LG) containing the fluorescent "age pigment" lipofuscin, melanoprotein granules (melanosomes, melanolysosomes) containing the screening pigment melanin and complex melanolipofuscin granules (MLG) containing both types of pigments simultaneously-melanin and lipofuscin. This review examines the functional role of pigment granules in the aging process and in the development of oxidative stress and associated pathologies in RPE cells. The focus is on the process of light-induced oxidative degradation of pigment granules caused by reactive oxygen species. The reasons leading to increased oxidative stress in RPE cells as a result of the oxidative degradation of pigment granules are considered. A mechanism is proposed to explain the phenomenon of age-related decline in melanin content in RPE cells. The essence of the mechanism is that when the lipofuscin part of the melanolipofuscin granule is exposed to light, reactive oxygen species are formed, which destroy the melanin part. As more melanolipofuscin granules are formed with age and the development of degenerative diseases, the melanin in pigmented epithelial cells ultimately disappears.

Keywords: aging; bisretinoids; lipofuscin; melanin; melanolipofuscin; oxidative stress; reactive oxygen species; retinal pigment epithelium.

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Conflict of interest statement

The authors declare no conflicts of interests.

Figures

Figure 1
Figure 1
Scheme of the structure of the fundus. RPE—retinal pigment epithelium; IPM—interphotoreceptor matrix [8].
Figure 2
Figure 2
Schematic illustration of lipofuscin and bisretinoid’s roles in the development of photooxidative stress in the RPE cell.
Figure 3
Figure 3
MLG from human RPE cells contain less melanin than MG. ESR spectra of MG (A) and MLG (B) from human RPE cells.
Figure 4
Figure 4
Scheme of the mechanisms involved in melanin degradation in the melanolipofuscin granule. Abbreviations: PMD—melanin degradation products, ROS—reactive oxygen species, LIP-ox—oxidized lipofuscin. (1.) Light in the presence of oxygen activates ROS generation mediated by lipofuscin fluorophores. The resulting ROS can oxidize both melanin, causing its degradation and the formation of PMD, and lipofuscin, causing the formation of reactive dicarbonyls. (2.) The resulting photosensitive melanin degradation products (PMDs) generate ROS when exposed to light and, in turn, cause the further degradation of melanin and lipofuscin. (3.) In a granule containing all three components, namely melanin, lipofuscin (bisretinoids) and PMD, light and ROS activate the transition of melanin to a high-energy state (melanin*) in which the excited pigment causes the degradation of lipofuscin [164,165].
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