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Aspartate aminotransferases (GOTs), located in the cytosol (GOT1) and mitochondria (GOT2), are key components of the malate-aspartate shuttle, which transfers reducing equivalents from cytosol to mitochondria. Previous work has implicated the GOTs as potential modulators of blinding retinal disease. To determine the roles of GOT1 and GOT2 in rod PRs, we generated rod PR-specific\n                  <jats:italic>Got1<\/jats:italic>\n                  or\n                  <jats:italic>Got2<\/jats:italic>\n                  conditional knockout mice (\n                  <jats:italic>Got1<\/jats:italic>\n                  or\n                  <jats:italic>Got2<\/jats:italic>\n                  cKO). We previously showed that\n                  <jats:italic>Got1<\/jats:italic>\n                  cKO causes PR degeneration and is accompanied by NADH accumulation and a decreased retinal NAD\n                  <jats:sup>+<\/jats:sup>\n                  \/NADH ratio. Here, we show that NADH oxidation via metabolic or genetic means prolongs PR survival in\n                  <jats:italic>Got1<\/jats:italic>\n                  cKO animals, implicating NADH accumulation, or reductive stress, as a key driver of PR degeneration. In contrast,\n                  <jats:italic>Got2<\/jats:italic>\n                  cKO causes minimal PR degeneration and alterations in retinal NADH and the NAD\n                  <jats:sup>+<\/jats:sup>\n                  \/NADH ratio that oppose reductive stress. Interestingly, GOT2, but not GOT1, is decreased in multiple models of PR degeneration, including retinal detachment (RD) where the NAD\n                  <jats:sup>+<\/jats:sup>\n                  \/NADH ratio favors a reductive state. Notably, loss of\n                  <jats:italic>Got2<\/jats:italic>\n                  in PRs demonstrates a neuroprotective effect after experimental RD suggesting decreased GOT2 expression may be part of a stress response to promote PR survival. Overall, this study illustrates the differential dependence on the GOTs for PR health, provides evidence that an overly reductive environment is detrimental to PR survival, and identifies GOT2 as a novel therapeutic target with potentially broad application in blinding diseases.\n                <\/jats:p>","DOI":"10.64898\/2026.04.05.716322","type":"posted-content","created":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T03:10:11Z","timestamp":1775617811000},"source":"Crossref","is-referenced-by-count":0,"title":["Redox imbalance dictates dependence on GOT1 versus GOT2 for rod photoreceptor health during aging and stress"],"prefix":"10.64898","author":[{"given":"Meini","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI, United States"},{"name":"Eye Center of Xiangya Hospital, Central South University, Changsha, Hunan, People\u2019s Republic of 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