{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T05:30:42Z","timestamp":1790400642707,"version":"4.1.0"},"reference-count":117,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,4,24]],"date-time":"2021-04-24T00:00:00Z","timestamp":1619222400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["EY30141"],"award-info":[{"award-number":["EY30141"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000888","name":"Keck Foundation","doi-asserted-by":"publisher","award":["60060"],"award-info":[{"award-number":["60060"]}],"id":[{"id":"10.13039\/100000888","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["EY026012"],"award-info":[{"award-number":["EY026012"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["EY028554"],"award-info":[{"award-number":["EY028554"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Elaine and Robert Larson Endowed Vision Research Chair, the Lindsay Family Foundation","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"Anonymous benefactor for AMD research","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"Ryan Initiative for Macular Research (RIMR),","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Glutathione (GSH) is present ubiquitously, and its role as a crucial cellular antioxidant in tissues, including the retina, is well established. GSH\u2019s antioxidant function arises from its ability to scavenge reactive oxygen species or to serve as an essential cofactor for GSH S-transferases and peroxidases. This review summarizes the general functions, retinal distribution, disorders linked to GSH deficiency, and the emerging role for mitochondrial GSH (mGSH) in retinal function. Though synthesized only in the cytosol, the presence of GSH in multiple cell organelles suggests the requirement for its active transport across organellar membranes. The localization and distribution of 2-oxoglutarate carrier (OGC) and dicarboxylate carrier (DIC), two recently characterized mitochondrial carrier proteins in RPE and retina, show that these transporters are highly expressed in human retinal pigment epithelium (RPE) cells and retinal layers, and their expression increases with RPE polarity in cultured cells. Depletion of mGSH levels via inhibition of the two transporters resulted in reduced mitochondrial bioenergetic parameters (basal respiration, ATP production, maximal respiration, and spare respiratory capacity) and increased RPE cell death. These results begin to reveal a critical role for mGSH in maintaining RPE bioenergetics and cell health. Thus, augmentation of mGSH pool under GSH-deficient conditions may be a valuable tool in treating retinal disorders, such as age-related macular degeneration and optic neuropathies, whose pathologies have been associated with mitochondrial dysfunction.<\/jats:p>","DOI":"10.3390\/antiox10050661","type":"journal-article","created":{"date-parts":[[2021,4,24]],"date-time":"2021-04-24T21:49:20Z","timestamp":1619300960000},"page":"661","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":103,"title":["Glutathione Metabolism and the Novel Role of Mitochondrial GSH in Retinal Degeneration"],"prefix":"10.3390","volume":"10","author":[{"given":"Parameswaran G.","family":"Sreekumar","sequence":"first","affiliation":[{"name":"The Stephen J. Ryan Initiative for Macular Research (RIMR), Doheny Eye Institute, Los Angeles, CA 90033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah A.","family":"Ferrington","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Neurosciences and Stem Cell Institute, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ram","family":"Kannan","sequence":"additional","affiliation":[{"name":"The Stephen J. Ryan Initiative for Macular Research (RIMR), Doheny Eye Institute, Los Angeles, CA 90033, USA"},{"name":"Stein Eye Institute, Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Sreekumar, P.G., Spee, C., Ryan, S.J., Cole, S.P.C., Kannan, R., and Hinton, D.R. (2012). Mechanism of RPE Cell Death in \u03b1-Crystallin Deficient Mice: A Novel and Critical Role for MRP1-Mediated GSH Efflux. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0033420"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Kwon, D.H., Lee, H., Park, C., Hong, S.-H., Hong, S.H., Kim, G.-Y., Cha, H.-J., Kim, S., Kim, H.-S., and Hwang, H.-J. (2019). Glutathione Induced Immune-Stimulatory Activity by Promoting M1-Like Macrophages Polarization via Potential ROS Scavenging Capacity. 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