{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T12:29:55Z","timestamp":1777984195510,"version":"3.51.4"},"reference-count":59,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T00:00:00Z","timestamp":1774656000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T00:00:00Z","timestamp":1774656000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["EY020542"],"award-info":[{"award-number":["EY020542"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000262","name":"Foundation Fighting Blindness","doi-asserted-by":"publisher","award":["BR\u2010CMM\u20100619\u20100763\u2010UIA"],"award-info":[{"award-number":["BR\u2010CMM\u20100619\u20100763\u2010UIA"]}],"id":[{"id":"10.13039\/501100000262","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Photoreceptors are highly energy\u2010demanding neurons, and disruption of photoreceptor signaling remodels retinal metabolism and contributes to degeneration, yet the pathways underlying these changes remain incompletely defined. Kv8.2 knockout (KO) mice, a model of KCNV2 retinopathy, exhibit impaired photoreceptor ion homeostasis and slow rod degeneration, providing an opportunity to investigate metabolic adaptation during progressive dysfunction. Untargeted metabolomic profiling was performed on retinas from wildtype (WT) and Kv8.2 KO mice at 1 and 13\u2009months of age. Principal component analysis revealed distinct profiles for aged Kv8.2 KO retinas compared with aged WT and young groups, while young WT and KO retinas were metabolically similar. The major changes in aged Kv8.2 KO retinas compared to aged WT were reduced nucleobases and nucleosides while the amino acids homocysteine, methionine, and serine were elevated. These are signature metabolites in one\u2010carbon metabolism, a metabolic hub influencing nucleotide metabolism, epigenic regulation, and anti\u2010oxidant defense. Supervised modeling showed that these one\u2010carbon\u2013related changes emerge early and progress with age in Kv8.2 KO retinas. Together, these findings implicate altered one\u2010carbon metabolism as a key mechanism in photoreceptor vulnerability and adaptation in slow retinal degeneration.<\/jats:p>\n                  <jats:p>\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\/jnc70420-gra-0001-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.70420","type":"journal-article","created":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T07:13:16Z","timestamp":1774681996000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Loss of Kv8.2 in the Mouse Retina Is Associated With Altered One\u2010Carbon Metabolism"],"prefix":"10.1111","volume":"170","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2494-0745","authenticated-orcid":false,"given":"Karina","family":"Kruth","sequence":"first","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences Carver College of Medicine, University of Iowa  Iowa Iowa USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0259-0652","authenticated-orcid":false,"given":"Sheila A.","family":"Baker","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences Carver College of Medicine, University of Iowa  Iowa Iowa USA"},{"name":"Department of Biochemistry and Molecular Biology, Carver College of Medicine University of Iowa  Iowa Iowa USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,3,28]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3349\/ymj.2004.45.5.776"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1023\/a:1023250721185"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/13816810.2020.1827441"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/347677a0"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.13610"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2025.110804"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.91141"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/IJG.0b013e31816f7631"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjo\u20102023\u2010323640"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.698985"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2016.08.009"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.202012687"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2440\u201017.2018"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2024.101244"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajo.2020.11.022"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.1983.01040010718003"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13578\u2010024\u201001224\u20106"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12886\u2010023\u201003149\u2010z"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1080\/13816810.2020.1766087"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0032\u201019.2019"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00965323"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep10585"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2004.05.003"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddab301"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22094877"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaophthalmol.2014.100"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1021\/jf070866p"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40662\u2010019\u20100167\u20109"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11457"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.65.1.6"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2025.110729"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13098\u2010018\u20100362\u20101"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1159\/000499020"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx449"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1023\/b:nere.0000010453.96832.97"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells11020214"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.2147\/OPTH.S77538"},{"key":"e_1_2_11_39_1","first-page":"2268","article-title":"MTHFR Gene C677T and A1298C Polymorphisms and Homocysteine Levels in Primary Open Angle and Primary Closed Angle Glaucoma","volume":"15","author":"Micheal S.","year":"2009","journal-title":"Molecular Vision"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2006.12.003"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1167\/tvst.13.8.8"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22052345"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom15020309"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003\u2010021\u201001765\u20103"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkae253"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/978\u20103\u2010319\u201055769\u20104_3"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2009.11.074"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2016.09.006"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.209759"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1007\/0\u2010387\u201030172\u20100_17"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2005.07.038"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2025.102127"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.3390\/metabo12121245"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2018.07.024"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom10020286"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2019.03.007"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.64.12.2"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1007\/978\u20103\u2010031\u201027681\u20101_67"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0007114507744409"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.62.10.9"}],"container-title":["Journal of Neurochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jnc.70420","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jnc.70420","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jnc.70420","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T06:13:01Z","timestamp":1777356781000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jnc.70420"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,28]]},"references-count":59,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1111\/jnc.70420"],"URL":"https:\/\/doi.org\/10.1111\/jnc.70420","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/JNC.70420\/v1\/decision1","asserted-by":"object"}]},"ISSN":["0022-3042","1471-4159"],"issn-type":[{"value":"0022-3042","type":"print"},{"value":"1471-4159","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,28]]},"assertion":[{"value":"2026-01-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-28","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70420"}}