Aging-US published this research paper on February 16, 2023 in Volume 15, Issue 6, entitled, “Knockout of AMD-associated gene POLDIP2 reduces mitochondrial superoxide in human retinal pigment epithelial cells” by researchers from the Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia; Ophthalmology, Department of Surgery, University of Melbourne, Melbourne, Victoria, Australia; O’Brien Institute Department, St Vincent’s Institute of Medical Research, Melbourne, Victoria, Australia; Departments of Surgery and Medicine, University of Melbourne, Melbourne, Victoria, Australia; Menzies Institute for Medical Research, School of Medicine, University of Tasmania, Hobart, Tasmania, Australia; Centre for Ophthalmology and Visual Science (Incorporating Lions Eye Institute), The University of Western Australia, Department of Ophthalmology, Royal Perth Hospital, Perth, Western Australia, Australia.
#openaccess #aging #research #retina #eyes #pigmentation #epithelial #cells #openscience #researchpaper #journal #publication #amd
DOI – https://doi.org/10.18632/aging.204522
Corresponding author – Raymond C.B. Wong – [email protected]
Abstract
Genetic and epidemiologic studies have significantly advanced our understanding of the genetic factors contributing to age-related macular degeneration (AMD). In particular, recent expression quantitative trait loci (eQTL) studies have highlighted POLDIP2 as a significant gene that confers risk of developing AMD. However, the role of POLDIP2 in retinal cells such as retinal pigment epithelium (RPE) and how it contributes to AMD pathology are unknown. Here we report the generation of a stable human RPE cell line ARPE-19 with POLDIP2 knockout using CRISPR/Cas, providing an in vitro model to investigate the functions of POLDIP2. We conducted functional studies on the POLDIP2 knockout cell line and showed that it retained normal levels of cell proliferation, cell viability, phagocytosis and autophagy. Also, we performed RNA sequencing to profile the transcriptome of POLDIP2 knockout cells. Our results highlighted significant changes in genes involved in immune response, complement activation, oxidative damage and vascular development. We showed that loss of POLDIP2 caused a reduction in mitochondrial superoxide levels, which is consistent with the upregulation of the mitochondrial superoxide dismutase SOD2. In conclusion, this study demonstrates a novel link between POLDIP2 and SOD2 in ARPE-19, which supports a potential role of POLDIP2 in regulating oxidative stress in AMD pathology.
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Keywords – aging, age-related macular degeneration, retina, CRISPR/Cas, mitochondria superoxide, POLDIP2
About Aging-US
Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways.
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