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Tissue hypoxia is a component of ischaemia and has devastating effects on the CNS, including neuronal death. Differences in blood supply, oxygen consumption, and the expression of excitatory receptors and oxygen\u2010binding proteins contribute to regional differences in the sensitivity of retinal neurons to hypoxia. Although highly variable and species\u2010dependent, the mammalian retina has the capacity to withstand the effects of oxygen deprivation through ischaemic preconditioning, where a brief, sublethal stimulus imparts protection against subsequent bouts of hypoxia or ischaemia. Decades of research have demonstrated that hypoxia\u2010 and anoxia\u2010tolerant ectotherms are adapted to survive weeks or months in the absence of oxygen without damage to the CNS, nor without the need for a preconditioning stimulus. Recent studies provide evidence that, in the retinas of tolerant animals, such as crucian carp, freshwater turtle and goldfish, prolonged oxygen deprivation elicits a reversible reduction in electroretinogram activity. Moreover, inhibitory interneurons of the outer retina involved in visual processing, called horizontal cells, sense hypoxia via mitochondrial ATP\u2010dependent K\n                    <jats:sup>+<\/jats:sup>\n                    channels and regulate intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    homeostasis. An understanding of how these mechanisms may protect the retina from hypoxia has only recently begun to emerge but may involve downregulation of excitatory receptor activity or release of the inhibitory neurotransmitter, GABA, to reduce neuronal activity and reduce the metabolic demands of the retina during oxygen deprivation.\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp16785-gra-0001-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1113\/jp287741","type":"journal-article","created":{"date-parts":[[2025,5,31]],"date-time":"2025-05-31T13:44:58Z","timestamp":1748699098000},"page":"6517-6531","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Adaptations to hypoxia in the vertebrate retina"],"prefix":"10.1113","volume":"603","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2111-1570","authenticated-orcid":false,"given":"Michael G.","family":"Jonz","sequence":"first","affiliation":[{"name":"Department of Biology &amp; Brain and Mind Research Institute University of Ottawa  Ottawa ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,5,31]]},"reference":[{"key":"e_1_2_2_2_1","first-page":"516","article-title":"Oxygen distribution in the macaque retina","volume":"34","author":"Ahmed J.","year":"1993","journal-title":"Investigative Ophthalmology & Visual Science"},{"key":"e_1_2_2_3_1","doi-asserted-by":"publisher","DOI":"10.1139\/y92-257"},{"key":"e_1_2_2_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(84)90828-X"},{"key":"e_1_2_2_5_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1984.sp015414"},{"key":"e_1_2_2_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0042-6989(85)90032-X"},{"key":"e_1_2_2_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0042-6989(87)90117-9"},{"key":"e_1_2_2_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2020.595064"},{"key":"e_1_2_2_9_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1971.sp009432"},{"key":"e_1_2_2_10_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1979.sp012715"},{"key":"e_1_2_2_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2021.11.055"},{"key":"e_1_2_2_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2006.11.008"},{"key":"e_1_2_2_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2023.1153934"},{"key":"e_1_2_2_14_1","doi-asserted-by":"publisher","DOI":"10.1242\/jeb.201.8.1141"},{"key":"e_1_2_2_15_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.69.031905.162529"},{"key":"e_1_2_2_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbpb.2017.11.015"},{"key":"e_1_2_2_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2011.11.003"},{"key":"e_1_2_2_18_1","first-page":"2376","article-title":"Hyperthermia and hypoxia increase tolerance of retinal ganglion cells to anoxia and excitotoxicity","volume":"37","author":"Caprioli J.","year":"1996","journal-title":"Investigative Ophthalmology & Visual Science"},{"key":"e_1_2_2_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0161-6420(82)34608-4"},{"key":"e_1_2_2_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/neu.480230915"},{"key":"e_1_2_2_21_1","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.2000.0125"},{"key":"e_1_2_2_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.25054"},{"key":"e_1_2_2_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2017.07.025"},{"key":"e_1_2_2_24_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00585.2016"},{"key":"e_1_2_2_25_1","doi-asserted-by":"publisher","DOI":"10.1242\/jeb.242634"},{"key":"e_1_2_2_26_1","doi-asserted-by":"publisher","DOI":"10.1242\/jeb.244238"},{"key":"e_1_2_2_27_1","doi-asserted-by":"publisher","DOI":"10.1152\/physiol.00027.2021"},{"key":"e_1_2_2_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2009.06196.x"},{"issue":"9","key":"e_1_2_2_29_1","first-page":"1481","article-title":"Micro\u2010electrode measurements and functional aspects of chloride activity in cyprinid fish retina: Extracellular activity and intracellular activities of L\u2010 and C\u2010type horizontal cells","volume":"27","author":"Djamgoz M. 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