Lipofuscins prepared by modification of photoreceptor cellsviaglycation or lipid peroxidation show the similar phototoxicity

Abstract

AIMTo investigate the effect of two ways of lipofuscin production (lipid peroxidation and glycation) on lipofuscin fluorescence characteristics and phototoxicity and to compare them with the properties of natural lipofuscin.METHODSModel lipofuscins were prepared on the basis of bovine photoreceptor outer segments (POS) with bisretinoid A2E addition. One set of samples was prepared from POS modified by lipid peroxidation, while another set from POS modified by glycation with fructose. Fluorescent properties and kinetics of photoinduced superoxide generation of model lipofuscins and human retinal pigment epithelium (RPE) lipofuscin were compared. The fluorescence spectra of samples were measured at 365 nm excitation wavelength and 380-650 emission wavelength.RESULTSThe fluorescence spectra of model lipofuscins are almost the same as the spectrum of natural lipofuscin. Visible light irradiation of both model lipofuscins and natural lipofuscin isolated from RPE cells leads to decrease of a fluorescence maximum at 550 nm and to appearance of a distinct, new maximum at 445-460 nm. The rate of photogeneration of reactive oxygen forms by both model lipofuscins was almost the same and approximately two times less than that of RPE lipofuscin granules.CONCLUSIONThese data suggest that fluorescent characteristics and phototoxicity of lipofuscin granules depend only to an insignificant degree on the oxidative modification of POS proteins and lipids, and generally are defined by the bisretinoid fluorophores contained in them.

Effects of A2E-Induced Oxidative Stress on Retinal Epithelial Cells: New Insights on Differential Gene Response and Retinal Dystrophies

“…Moreover, lipid peroxidation is also responsible for A2E cleavage that releases cytotoxic reactive aldehydes. These reactive species could affect the lipid membranes fluidity and can damage the DNA and the cellular proteins [24]. On these bases, it was hypothesized that lipofuscin, A2E and its oxidized metabolites could accumulate if the cellular antioxidant system is unable to fight the oxidative-damaged lipids in rods and cones.…”

Oxidized Lipids Decrease Phagocytic Activity of ARPE‐19 Cells In Vitro

“…It has been shown that photoreactivity and phototoxicity of the chloroform non‐soluble fraction of human RPE lipofuscin granules increases with age of donors . On the other hand, Dontsov et al showed that photoreactivity of model Lf represented by oxidized POS with addition of A2E resembled that of natural RPE Lf and depended on the degree of oxidative modifications of POS proteins and lipids . Partly oxidized lipids, which are present in POS, especially in mature discs, are also present in Folch’ extract of bovine neural retinas, used in this research.…”

“…[54] On the other hand, Dontsov et al showed that photoreactivity of model Lf represented by oxidized POS with addition of A2E resembled that of natural RPE Lf and depended on the degree of oxidative modifications of POS proteins and lipids. [55] Partly oxidized lipids, which are present in POS, especially in mature discs, are also present in Folch' extract of bovine neural retinas, used in this research. The Folch' extraction is regarded as one of the most reliable methods for isolation of a broad range of lipid classes from biological materials.…”

The effect of A2E on lysosome membrane permeability during blue light-induced human RPEs apoptosis

“…It was composed of bimolecular all-trans-retinal and monomolecular ethanolamine [ 22 ]. The precursor of A2E was formed in the rodoutersegmeni (ROS); however, A2E itself existed in the phagolysosomes of RPEs [ 23 ]. In consequence, we inferred that A2E might be the initiation factor of RPEs apoptosis.…”