Abstract
Age-related macular degeneration (AMD) is a degenerative retinal disease and one of major causes of irreversible vision loss. AMD has been linked to several pathological factors, such as oxidative stress and inflammation. Moreover, Aβ (1–42) oligomers have been found in drusen, the extracellular deposits that accumulate beneath the retinal pigmented epithelium in AMD patients. Hereby, we investigated the hypothesis that treatment with 1,25(OH) 2D3 (vitamin D3) and meso-zeaxathin, physiologically present in the eye, would counteract the toxic effects of three different insults on immortalized human retinal pigmented epithelial cells (ARPE-19). Specifically, ARPE-19 cells have been challenged with Aβ (1–42) oligomers, H2O2, LPS, and TNF-α, respectively. In the present study, we demonstrated that the combination of 1,25(OH)2D3 and meso-zeaxanthin significantly counteracted the cell damage induced by the three insults, at least in these in vitro integrated paradigms of AMD. These results suggest that combination of 1,25(OH)2D3 and meso-zeaxathin could be a useful approach to contrast pathological features of AMD, such as retinal inflammation and oxidative stress.
Highlights
Age-related macular degeneration (AMD) is a progressive neurodegenerative and multifactorial disease that if not treated or managed can impair irreversibly the visual function (Cascella et al, 2014; Pennington and DeAngelis, 2016) in the elderly population (Nowak, 2006)
ARPE-19 cells were challenged with four different stimuli: amyloid-β oligomers (1 and 2.5 μM; amyloid β-protein 1–42 HFIP-treated, Bachem H-7442.0100) (Calafiore et al, 2012; Caruso et al, 2021), hydrogen peroxide (400 μM H2O2), LPS (150 ng/ml and 10 μg/ml, Enzo ALX581–010-L001, Farmingdale, NY), and tumor necrosis-alpha (TNF-α) (10 ng/ml, Thermo Fisher Scientific, Carlsbad, CA), in order to simulate retinal degeneration, retinal oxidative stress, and early and late inflammation, respectively. 1,25(OH)2D3, MZ, and the combo were added to the medium containing negative stimuli
Preliminary studies were carried out with the MTT assay to evaluate Aβoligomer toxicity on ARPE-19 cells, and we found that 1 μM Aβoligomers for 48 h induced roughly 17% cell death
Summary
Age-related macular degeneration (AMD) is a progressive neurodegenerative and multifactorial disease that if not treated or managed can impair irreversibly the visual function (Cascella et al, 2014; Pennington and DeAngelis, 2016) in the elderly population (usually older than 60 years) (Nowak, 2006). In the macula of AMD patients, between the retinal pigment epithelium (RPE) and Bruch’s membrane, lesions named drusen have been found. These lesions are characterized by accumulation of extracellular material, lipid, and protein aggregates. Wet AMD is characterized by overexpression of the vascular endothelial growth factor (VEGF-A), which leads to the breakdown of the blood–retinal barrier and choroidal neovascularization (Kauppinen et al, 2016). Retinal degeneration in wet AMD is tightly linked to choroidal neovascularization (CNV) and growth of leaky blood vessels under the macula, due to overproduction of pro-angiogenic factors (VEGF family) and inflammatory cytokines. The altered cellular homeostasis in RPE cells, related to ROS overproduction, can be induced by several factors, such as, aging process, light exposure, diet, and cigarette smoking
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