{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T18:50:39Z","timestamp":1791399039354,"version":"4.3.3"},"reference-count":102,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"41","funder":[{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["310030_200798"],"award-info":[{"award-number":["310030_200798"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["212508"],"award-info":[{"award-number":["212508"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["219656"],"award-info":[{"award-number":["219656"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["10006601"],"award-info":[{"award-number":["10006601"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Hermann Kurz Foundation"},{"name":"Gudrun-Ulrika Foundation"},{"DOI":"10.13039\/501100020884","name":"Agencia Nacional de Investigaci\u00f3n y Desarrollo","doi-asserted-by":"publisher","award":["1230145"],"award-info":[{"award-number":["1230145"]}],"id":[{"id":"10.13039\/501100020884","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2026,10,9]]},"abstract":"<jats:p>The retina metabolizes glucose into lactate, a hallmark of aerobic glycolysis known as the Warburg effect. Although evidence points to rod photoreceptors as the primary source of aerobic glycolysis, a comparison of the energy metabolism in different retinal neurons has yet to be performed. We combined two-photon fluorescence lifetime imaging of biosensors with pharmacological protocols to analyze metabolic dynamics in healthy and diseased rod photoreceptors and RBPMS-positive ganglion and calretinin-positive amacrine cells. Our data reveal distinct metabolic profiles among retinal neurons, identify rods as the drivers of aerobic glycolysis, demonstrate that inner retinal neurons rely on oxidative phosphorylation, show that rods need both glycolysis and oxidative phosphorylation to maintain ATP levels, and suggest that rods can metabolize lactate. A mutation causing retinitis pigmentosa increases lactate production in rods but changes the energy metabolism only subtly otherwise. Our results improve the understanding of retinal physiology and are relevant for pathologies involving imbalanced energy metabolism.<\/jats:p>","DOI":"10.1126\/sciadv.aeg8687","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T17:58:33Z","timestamp":1791395913000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Rod photoreceptors have a dual dependency on both aerobic glycolysis and OXPHOS and diverge metabolically from other retinal neurons"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4299-7270","authenticated-orcid":true,"given":"Gabriele M.","family":"W\u00f6genstein","sequence":"first","affiliation":[{"name":"Laboratory for Retinal Cell Biology, Department of Ophthalmology, University Hospital Zurich, University of Zurich, Wagistrasse 14, Schlieren, 8952, Zurich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0431-9866","authenticated-orcid":true,"given":"Luca","family":"Ravotto","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology and Neuroscience Center Zurich, University and ETH Zurich, Winterthurerstr. 190, 8057, Zurich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vyara","family":"Todorova","sequence":"additional","affiliation":[{"name":"Laboratory for Retinal Cell Biology, Department of Ophthalmology, University Hospital Zurich, University of Zurich, Wagistrasse 14, Schlieren, 8952, Zurich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-1400-0214","authenticated-orcid":true,"given":"Rachel M.","family":"Meister","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology and Neuroscience Center Zurich, University and ETH Zurich, Winterthurerstr. 190, 8057, Zurich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marijana","family":"Samardzija","sequence":"additional","affiliation":[{"name":"Laboratory for Retinal Cell Biology, Department of Ophthalmology, University Hospital Zurich, University of Zurich, Wagistrasse 14, Schlieren, 8952, Zurich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6623-4833","authenticated-orcid":true,"given":"L. Felipe","family":"Barros","sequence":"additional","affiliation":[{"name":"Centro de Estudios Cientificos-CECs, Valdivia, Chile."},{"name":"Facultad de Medicina, Universidad San Sebasti\u00e1n, Valdivia, Chile."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Weber","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology and Neuroscience Center Zurich, University and ETH Zurich, Winterthurerstr. 190, 8057, Zurich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9318-4352","authenticated-orcid":true,"given":"Christian","family":"Grimm","sequence":"additional","affiliation":[{"name":"Laboratory for Retinal Cell Biology, Department of Ophthalmology, University Hospital Zurich, University of Zurich, Wagistrasse 14, Schlieren, 8952, Zurich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1139\/y92-257"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.2147\/EB.S9078"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01504608"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.77.6.667"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-vision-100419-115156"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00410.2018"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-201X.1997.00131.x"},{"key":"e_1_3_2_9_2","first-page":"48","article-title":"Glucose metabolism in cat outer retina. Effects of light and hyperoxia","volume":"38","author":"Wang L.","year":"1997","unstructured":"L. Wang, M. Kondo, A. Bill, Glucose metabolism in cat outer retina. Effects of light and hyperoxia. Invest. Ophthalmol. Vis. Sci. 38, 48\u201355 (1997).","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.28899"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1412441111"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.15-17962"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.25946"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-018-0296-4"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.04.111"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/pnasnexus\/pgad038"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22073689"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-201X.1997.00030.x"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2020.100881"},{"key":"e_1_3_2_20_2","first-page":"847","article-title":"The cellular and compartmental profile of mouse retinal glycolysis, tricarboxylic acid cycle, oxidative phosphorylation, and \u223cP transferring kinases","volume":"22","author":"Rueda E. M.","year":"2016","unstructured":"E. M. Rueda, J. E. Johnson Jr., A. Giddabasappa, A. Swaroop, M. J. Brooks, I. Sigel, S. Y. Chaney, D. A. Fox, The cellular and compartmental profile of mouse retinal glycolysis, tricarboxylic acid cycle, oxidative phosphorylation, and \u223cP transferring kinases. Mol. Vis. 22, 847\u2013885 (2016).","journal-title":"Mol. Vis."},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2017.11.002"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-18098-z"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-018-0712-9"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep37727"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-03103-7"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1311193110"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-023-00602-x"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2024.106794"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2022.109352"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2421978122"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbpa.2015.05.024"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2014.06.003"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M309881200"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/gt.2010.56"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature12354"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)99072-1"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.16-19393"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1383-8121(00)80009-3"},{"key":"e_1_3_2_39_2","doi-asserted-by":"crossref","unstructured":"T. Euler K. Franke T. Baden Studying a light sensor with light: Multiphoton imaging in the retina. in vol. 148 Multiphoton Microscopy. Neuromethods E. Hartveit Ed (Humana New York NY 2019) pp. 225\u2013250.","DOI":"10.1007\/978-1-4939-9702-2_10"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.12.7035"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1410162111"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02737085"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0904764106"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/0926-6593(66)90031-2"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2018.11.005"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5311-10.2011"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnene.2010.00026"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.91141"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.100747.3"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1604572113"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20091515"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2008.05250.x"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2011.08.012"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2015.6593"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cophys.2018.03.011"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-30685-x"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-022-01151-3"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.63.4.1"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.11.043"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.209759"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1012100"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.698985"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-031-27681-1_64"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41589-022-01012-8"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.15878"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.18632\/aging.100329"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.23994"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2024.109916"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.23583"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.22.10625"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2015.10.010"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.15-18441"},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.2337\/diab.23.3.221"},{"key":"e_1_3_2_74_2","first-page":"106","article-title":"Retinal glycogen","volume":"59","author":"Kuwabara T.","year":"1961","unstructured":"T. Kuwabara, D. Cogan, Retinal glycogen. Trans. Am. Ophthalmol. Soc. 59, 106\u2013110 (1961).","journal-title":"Trans. Am. Ophthalmol. Soc."},{"key":"e_1_3_2_75_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.47.1.263"},{"key":"e_1_3_2_76_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gt.3301905"},{"key":"e_1_3_2_77_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2013.07.001"},{"key":"e_1_3_2_78_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddac013"},{"key":"e_1_3_2_79_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1448"},{"key":"e_1_3_2_80_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.15-17901"},{"key":"e_1_3_2_81_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00253.2009"},{"key":"e_1_3_2_82_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2022.1038421"},{"key":"e_1_3_2_83_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.03.022"},{"key":"e_1_3_2_84_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.06.093"},{"key":"e_1_3_2_85_2","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-021-01765-3"},{"key":"e_1_3_2_86_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41433-021-01726-4"},{"key":"e_1_3_2_87_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2234"},{"key":"e_1_3_2_88_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.03.023"},{"key":"e_1_3_2_89_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI86905"},{"key":"e_1_3_2_90_2","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.88.4.521"},{"key":"e_1_3_2_91_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2001776117"},{"key":"e_1_3_2_92_2","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhw366"},{"key":"e_1_3_2_93_2","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-025-08677-6"},{"key":"e_1_3_2_94_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0062097"},{"key":"e_1_3_2_95_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.17-22281"},{"key":"e_1_3_2_96_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI154619"},{"key":"e_1_3_2_97_2","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2015.333"},{"key":"e_1_3_2_98_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.06-5895fje"},{"key":"e_1_3_2_99_2","doi-asserted-by":"publisher","DOI":"10.1364\/BOE.6.004228"},{"key":"e_1_3_2_100_2","doi-asserted-by":"publisher","DOI":"10.1186\/1475-925X-2-13"},{"key":"e_1_3_2_101_2","first-page":"025009","article-title":"A low-cost FPGA-based approach for pile-up corrected high-speed in vivo FLIM imaging","volume":"12","author":"Moros F. V.","year":"2025","unstructured":"F. V. Moros, D. Amiet, R. M. Meister, A. von Faber-Castell, M. Wyss, A. S. Saab, P. Zbinden, B. Weber, L. Ravotto, A low-cost FPGA-based approach for pile-up corrected high-speed in vivo FLIM imaging. Neurophotonics 12, 025009 (2025).","journal-title":"Neurophotonics"},{"key":"e_1_3_2_102_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0070687"},{"key":"e_1_3_2_103_2","doi-asserted-by":"publisher","DOI":"10.1134\/S0022093023040142"}],"container-title":["Science Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciadv.aeg8687","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T18:00:43Z","timestamp":1791396043000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciadv.aeg8687"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,9]]},"references-count":102,"journal-issue":{"issue":"41","published-print":{"date-parts":[[2026,10,9]]}},"alternative-id":["10.1126\/sciadv.aeg8687"],"URL":"https:\/\/doi.org\/10.1126\/sciadv.aeg8687","relation":{},"ISSN":["2375-2548"],"issn-type":[{"value":"2375-2548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,9]]},"assertion":[{"value":"2026-03-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-31","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eaeg8687"}}