Journal
CELLS
Volume 12, Issue 1, Pages -Publisher
MDPI
DOI: 10.3390/cells12010043
Keywords
geographic atrophy; low-density lipoprotein receptor; oxidative stress; inflammation; retinal pigment epithelium; retinal degeneration; retinal function
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Lipid peroxidation caused by oxidative stress is a major factor in age-related macular degeneration (AMD). This study aims to investigate the role of LDLR in the NaIO3-induced model of dry AMD. The results indicate that LDLR loss leads to lipid accumulation and impaired retinal function, which may contribute to the development of AMD.
Lipid peroxidation from oxidative stress is considered a major contributor to age-related macular degeneration (AMD). The retina is abundant with circulating low-density lipoproteins (LDL), which are taken up by LDL receptor (LDLR) in the RPE and Muller cells. The purpose of this study is to investigate the role of LDLR in the NaIO3-induced model of dry AMD. Confluent primary human RPE (hRPE) and LDLR-silenced ARPE-19 cells were stressed with 150 mu M tert-butyl hydroperoxide (tBH) and caspase 3/7 activation was determined. WT and Ldlr (-/-) mice were administered NaIO3 (20 mg/kg) intravenously. On day 7, fundus imaging, OCT, ERG, and retinal thickness were measured. Histology, TUNEL, cleaved caspase 3 and lipid accumulation were assessed. Treatment of hRPE with tBH markedly decreased LDLR expression. Caspase 3/7 activation was significantly increased in LDLR-silenced ARPE-19 cells treated with tBH. In Ldlr (-/-) mice, NaIO3 administration resulted in significant (a) retinal thinning, (b) compromised photoreceptor function, (c) increased percentage of cleaved caspase 3 positive and apoptotic cells, and (d) increased lipid droplet accumulation in the RPE, Bruch membrane, choroid, and sclera, compared to WT mice. Our findings imply that LDLR loss leads to lipid accumulation and impaired retinal function, which may contribute to the development of AMD.
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