Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Crosstalk between the Rod Outer Segments and Retinal Pigmented Epithelium in the Generation of Oxidative Stress in an In Vitro Model.

Version 1 : Received: 28 June 2023 / Approved: 29 June 2023 / Online: 29 June 2023 (10:54:50 CEST)

A peer-reviewed article of this Preprint also exists.

Ravera, S.; Bertola, N.; Puddu, A.; Bruno, S.; Maggi, D.; Panfoli, I. Crosstalk between the Rod Outer Segments and Retinal Pigmented Epithelium in the Generation of Oxidative Stress in an In Vitro Model. Cells 2023, 12, 2173. Ravera, S.; Bertola, N.; Puddu, A.; Bruno, S.; Maggi, D.; Panfoli, I. Crosstalk between the Rod Outer Segments and Retinal Pigmented Epithelium in the Generation of Oxidative Stress in an In Vitro Model. Cells 2023, 12, 2173.

Abstract

Dysfunction of the retinal pigment epithelium (RPE) is associated with several diseases characterized by retinal degeneration, such as diabetic retinopathy (DR). However, it has recently been proposed that outer retinal neurons also participate in the damage triggering. Therefore, we have evaluated possible crosstalk between RPE and photoreceptors in priming and maintaining oxi-dative damage of the RPE. For this purpose, we used ARPE-19 cells as a model of human RPE, grown in normal (NG, 5.6 mM) or high glucose (HG, 25 mM), and unoxidized (UOx) or oxidized (Ox) mammalian retinal rod outer segments (OS). ARPE-19 cells were efficient at phagocytizing rod OS in both NG and HG settings. However, in HG, ARPE-19 cells treated with Ox-rod OS accumulated MDA and lipofuscins and displayed altered LC3, GRP78, and Caspase 8 expression, compared to untreated and UOx-rod OS-treated cells. Data suggest that early oxidative damage may originate from the photoreceptors and subsequently extend to the RPE, providing a new perspective to the idea that retinal degeneration depends solely on a redox alteration of the RPE.

Keywords

retinal pigmented epithelium; rod outer segments; aerobic metabolism; oxidative stress; lipofuscin; antioxidants; diabetic retinopathy; hyperglycemia.

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

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