{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T01:43:37Z","timestamp":1789177417189,"version":"build-2803163510"},"reference-count":64,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2021,4,9]],"date-time":"2021-04-09T00:00:00Z","timestamp":1617926400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1145121"],"award-info":[{"award-number":["APP1145121"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007811","name":"Sydney Medical School Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007811","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001108","name":"Ophthalmic Research Institute of Australia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001108","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Glia"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The importance of M\u00fcller glia for retinal homeostasis suggests that they may have vulnerabilities that lead to retinal disease. Here, we studied the effect of selectively knocking down key metabolic genes in M\u00fcller glia on photoreceptor health. Immunostaining indicated that murine M\u00fcller glia expressed insulin receptor (IR), hexokinase 2 (HK2) and phosphoglycerate dehydrogenase (PHGDH) but very little pyruvate dehydrogenase E1 alpha 1 (PDH\u2010E1\u03b1) and lactate dehydrogenase A (LDH\u2010A). We crossed M\u00fcller glial cell\u2010CreER (MC\u2010CreER) mice with transgenic mice carrying a floxed IR, HK2, PDH\u2010E1\u03b1, LDH\u2010A, or PHGDH gene to study the effect of selectively knocking down key metabolic genes in M\u00fcller glia cells on retinal health. Selectively knocking down IR, HK2, or PHGDH led to photoreceptor degeneration and reduced electroretinographic responses. Supplementing exogenous\n                    <jats:sc>l<\/jats:sc>\n                    \u2010serine prevented photoreceptor degeneration and improved retinal function in MC\u2010PHGDH knockdown mice. We unexpectedly found that the levels of retinal serine and glycine were not reduced but, on the contrary, highly increased in MC\u2010PHGDH knockdown mice. Moreover, dietary serine supplementation, while rescuing the retinal phenotypes caused by genetic deletion of PHGDH in M\u00fcller glial cells, restored retinal serine and glycine homeostasis probably through regulation of serine transport. No retinal abnormalities were observed in MC\u2010CreER mice crossed with PDH\u2010E1\u03b1\u2010 or LDH\u2010A\u2010floxed mice despite Cre expression. Our findings suggest that M\u00fcller glia do not complete glycolysis but use glucose to produce serine to support photoreceptors. Supplementation with exogenous serine is effective in preventing photoreceptor degeneration caused by PHGDH deficiency in M\u00fcller glia.\n                  <\/jats:p>","DOI":"10.1002\/glia.24005","type":"journal-article","created":{"date-parts":[[2021,4,9]],"date-time":"2021-04-09T10:14:57Z","timestamp":1617963297000},"page":"1966-1986","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Effect of selectively knocking down key metabolic genes in M\u00fcller glia on photoreceptor health"],"prefix":"10.1002","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7975-7409","authenticated-orcid":false,"given":"Weiyong","family":"Shen","sequence":"first","affiliation":[{"name":"Discipline of Ophthalmology Sydney Medical School, The University of Sydney, Save Sight Institute  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"So\u2010Ra","family":"Lee","sequence":"additional","affiliation":[{"name":"Discipline of Ophthalmology Sydney Medical School, The University of Sydney, Save Sight Institute  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashish Easow","family":"Mathai","sequence":"additional","affiliation":[{"name":"Discipline of Ophthalmology Sydney Medical School, The University of Sydney, Save Sight Institute  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Discipline of Ophthalmology Sydney Medical School, The University of Sydney, Save Sight Institute  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhai","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Biochemistry West Virginia University  Morgantown West Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle X.","family":"Yam","sequence":"additional","affiliation":[{"name":"Discipline of Ophthalmology Sydney Medical School, The University of Sydney, Save Sight Institute  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Pye","sequence":"additional","affiliation":[{"name":"Discipline of Ophthalmology Sydney Medical School, The University of Sydney, Save Sight Institute  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nigel L.","family":"Barnett","sequence":"additional","affiliation":[{"name":"Clem Jones Centre for Regenerative Medicine, Faculty of Health Science &amp; Medicine Bond University  Gold Coast Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cassie L.","family":"Rayner","sequence":"additional","affiliation":[{"name":"Clem Jones Centre for Regenerative Medicine, Faculty of Health Science &amp; Medicine Bond University  Gold Coast Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Zhu","sequence":"additional","affiliation":[{"name":"Discipline of Ophthalmology Sydney Medical School, The University of Sydney, Save Sight Institute  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James B.","family":"Hurley","sequence":"additional","affiliation":[{"name":"Department of Biochemistry University of Washington  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pankaj","family":"Seth","sequence":"additional","affiliation":[{"name":"Division of Interdisciplinary Medicine Beth Israel Deaconess Medical Center and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshio","family":"Hirabayashi","sequence":"additional","affiliation":[{"name":"Sako Cellular Informatics Laboratory RIKEN Cluster for Pioneering Research  Wako Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeki","family":"Furuya","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Biotechnology Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark C.","family":"Gillies","sequence":"additional","affiliation":[{"name":"Discipline of Ophthalmology Sydney Medical School, The University of Sydney, Save Sight Institute  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,4,9]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1080549"},{"key":"e_1_2_9_3_1","first-page":"1311","article-title":"Comparison of expression profile of neurotrophins and their receptors in primary and transformed rat retinal ganglion cells","volume":"13","author":"Agarwal N.","year":"2007","journal-title":"Molecular Vision"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2014.02.004"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00418-010-0752-4"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.51.12.3384"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/ceo.12050"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.15-17962"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.25946"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1986.tb00686.x"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.mie.2015.04.002"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.18-24289"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1812941116"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abb8598"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9136(199712)14:12<1044::AID-DIA508>3.0.CO;2-F"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.23583"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.11.103"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2012.11.002"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.10-7139"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.28899"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aat9528"},{"issue":"6","key":"e_1_2_9_22_1","first-page":"2887","article-title":"GLUT1 glucose transporter expression in the diabetic and nondiabetic human eye","volume":"35","author":"Kumagai A. 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