{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T06:12:50Z","timestamp":1791267170710,"version":"4.1.0"},"reference-count":73,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:00:00Z","timestamp":1773792000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:00:00Z","timestamp":1773792000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Glaucoma is a leading cause of irreversible blindness worldwide. One hallmark of glaucoma is the degeneration of retinal ganglion cells (RGCs). In this study, a dual role for growth hormone\u2010releasing hormone receptor (GHRHR) modulation under glaucoma\u2010relevant conditions and complementary injury paradigms involving the RGCs is identified. Using acute IOP elevation (retinal ischemia\u2010reperfusion), chronic ocular hypertension (microbead\u2010induced), and traumatic axonal injury (optic nerve crush) models, we show that GHRHR deficiency preserves RGC survival and uniquely restores visual functions\u2014contrasting with GHRHR activation, which solely promotes cellular survival. Single\u2010cell transcriptomic analysis uncovers RGC\u2010specific alterations in genes associated with ferroptosis, lipid metabolism, oxidative stress, and mitochondrial dynamics. At the mechanistic level, GHRHR deficiency prevents the pathological downregulation of key anti\u2010ferroptotic mediators GPX4 and FTH1 while suppressing pro\u2010ferroptotic factors ACSL4 caused by glaucomatous neurodegeneration. This multifaceted regulation attenuated iron accumulation, lipid peroxidation, and reactive oxygen species (ROS) accumulation, effects that are diminished by the ferroptosis inducer RSL3. Notably, in mitochondria damaged primary RGCs, pharmacological GHRHR inhibition replicates these benefits, reducing lipid peroxidation and mitochondrial ROS to bolster RGC survival. Collectively, these findings establish GHRHR inhibition as a potent therapeutic strategy for glaucomatous neurodegeneration, synergistically rescuing both structural and functional integrity of the retina.<\/jats:p>","DOI":"10.1002\/advs.202522929","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T19:18:03Z","timestamp":1773861483000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["GHRHR Deficiency Enhances Retinal Ganglion Cell Survival and Visual Functions in Experimental Glaucoma by Inhibiting Ferroptosis"],"prefix":"10.1002","author":[{"given":"Yan","family":"Tong","sequence":"first","affiliation":[{"name":"Department of Ophthalmology &amp; Visual Sciences The Chinese University of Hong Kong  Hong Kong China"},{"name":"Joint Shantou International Eye Center of Shantou University and The Chinese University of Hong Kong  Shantou China"},{"name":"Department of Ophthalmology Shenzhen People's Hospital (The First Affiliated Hospital, Southern University of Science and Technology; The Second Clinical Medical College, Jinan University) Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming Ho","family":"Yam","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences The Chinese University of Hong Kong  Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology &amp; Visual Sciences The Chinese University of Hong Kong  Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology &amp; Visual Sciences The Chinese University of Hong Kong  Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linbin","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology &amp; Visual Sciences The Chinese University of Hong Kong  Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yolanda Wong Ying","family":"Yip","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology &amp; Visual Sciences The Chinese University of Hong Kong  Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo Man","family":"Ho","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology &amp; Visual Sciences The Chinese University of Hong Kong  Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hemlata","family":"Bisnauthsing","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology &amp; Visual Sciences The Chinese University of Hong Kong  Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahui","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology &amp; Visual Sciences The Chinese University of Hong Kong  Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Kong","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology &amp; Visual Sciences The Chinese University of Hong Kong  Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shushu","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology &amp; Visual Sciences The Chinese University of Hong Kong  Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changzhen","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology &amp; Visual Sciences The Chinese University of Hong Kong  Hong Kong China"},{"name":"Joint Shantou International Eye Center of Shantou University and The Chinese University of Hong Kong  Shantou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl K.H.","family":"So","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences The Chinese University of Hong Kong  Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joaquim S.L.","family":"Vong","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences The Chinese University of Hong Kong  Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling\u2010Ping","family":"Cen","sequence":"additional","affiliation":[{"name":"Joint Shantou International Eye Center of Shantou University and The Chinese University of Hong Kong  Shantou China"},{"name":"Shantou University Medical College  Shantou Guangdong China"},{"name":"Guangdong Provincial Key Laboratory of Medical Immunology and Molecular Diagnostics, The First Dongguan Affiliated Hospital School of Medical University  Dongguan China"},{"name":"Dongguan Guangming Eye Hospital  Dongguan Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming\u2010Ming","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Shenzhen People's Hospital (The First Affiliated Hospital, Southern University of Science and Technology; The Second Clinical Medical College, Jinan University) Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khazeema","family":"Yousaf","sequence":"additional","affiliation":[{"name":"Pakistan Pediatric Association  Punjab Pakistan"},{"name":"Department of Biotechnology Lahore College for Women University  Lahore Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mai Har","family":"Sham","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences The Chinese University of Hong Kong  Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sun On","family":"Chan","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences The Chinese University of Hong Kong  Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Poemen P.","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology &amp; Visual Sciences The Chinese University of Hong Kong  Hong Kong China"},{"name":"Joint Shantou International Eye Center of Shantou University and The Chinese University of Hong Kong  Shantou China"},{"name":"Lam Kin Chung. Jet King\u2010Shing Ho Glaucoma Treatment and Research Centre The Chinese University of Hong Kong  Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi Pui","family":"Pang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology &amp; Visual Sciences The Chinese University of Hong Kong  Hong Kong China"},{"name":"Joint Shantou International Eye Center of Shantou University and The Chinese University of Hong Kong  Shantou China"},{"name":"Lam Kin Chung. Jet King\u2010Shing Ho Glaucoma Treatment and Research Centre The Chinese University of Hong Kong  Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clement C.","family":"Tham","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology &amp; Visual Sciences The Chinese University of Hong Kong  Hong Kong China"},{"name":"Joint Shantou International Eye Center of Shantou University and The Chinese University of Hong Kong  Shantou China"},{"name":"Lam Kin Chung. Jet King\u2010Shing Ho Glaucoma Treatment and Research Centre The Chinese University of Hong Kong  Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing Na","family":"He","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology &amp; Visual Sciences The Chinese University of Hong Kong  Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology &amp; Visual Sciences The Chinese University of Hong Kong  Hong Kong China"},{"name":"Department of Ophthalmology, Affiliated Hangzhou First People's Hospital, School of Medicine Westlake University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2903-3247","authenticated-orcid":false,"given":"Wai Kit","family":"Chu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology &amp; Visual Sciences The Chinese University of Hong Kong  Hong Kong China"},{"name":"Joint Shantou International Eye Center of Shantou University and The Chinese University of Hong Kong  Shantou China"},{"name":"Lam Kin Chung. Jet King\u2010Shing Ho Glaucoma Treatment and Research Centre The Chinese University of Hong Kong  Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,18]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2014.3192"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2014.05.013"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2024.101261"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.66.5.26"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2019\u201000111"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2018.22"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010020\u201018945\u20100"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncpendmet0677"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41574\u2010024\u201001052\u20101"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1210\/endocr\/bqac209"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1904532117"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1421815112"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1525520113"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010023\u201039023\u20101"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ghir.2011.05.008"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.18\u201024751"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1920834118"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.06.003"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.03.042"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418\u2010022\u201001046\u20104"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974\u2010022\u201002621\u20109"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2022.102541"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0793\u2010227"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600\u20100463.2003.11101251.x"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.18\u201026216"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10633\u2010014\u20109448\u20108"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/0896\u20106273(88)90127\u20104"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.202105043"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1523\/jneurosci.1947\u201008.2008"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010024\u201049202\u20103"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0110722"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/smll.202302962"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/88443"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.06\u20100925"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1076\/ceyr.26.5.371.15439"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.21899"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.09\u20103717"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2011.88"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13186"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.122.060257"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.4103\/1673\u20105374.350196"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.eye.6701565"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0099299"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.03\u20100872"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418\u2010019\u20100299\u20104"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.11.048"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010019\u20101705\u20102"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010022\u201005022\u20103"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.100504"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2017.01.009"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1618582114"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2308342120"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380\u2010021\u201001228\u20105"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20210518"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419\u2010023\u201005716\u20100"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1186\/s43556\u2010025\u201000317\u2010z"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42255\u2010025\u201001313\u2010x"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2020.102535"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1002\/cti2.1180"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10571\u2010018\u20100634\u20101"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.132747"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202310227"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2015.06.011"},{"key":"e_1_2_11_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2020.12.007"},{"key":"e_1_2_11_66_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2109600118"},{"key":"e_1_2_11_67_1","doi-asserted-by":"publisher","DOI":"10.1038\/364208a0"},{"key":"e_1_2_11_68_1","doi-asserted-by":"publisher","DOI":"10.3791\/54065\u2010v"},{"key":"e_1_2_11_69_1","doi-asserted-by":"publisher","DOI":"10.3791\/52400\u2010v"},{"key":"e_1_2_11_70_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.09\u20103921"},{"key":"e_1_2_11_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2013.12.010"},{"key":"e_1_2_11_72_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.17\u201022436"},{"key":"e_1_2_11_73_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010022\u201000935\u2010x"},{"key":"e_1_2_11_74_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0806114105"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202522929","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.202522929","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202522929","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T19:18:04Z","timestamp":1773861484000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202522929"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,18]]},"references-count":73,"alternative-id":["10.1002\/advs.202522929"],"URL":"https:\/\/doi.org\/10.1002\/advs.202522929","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,18]]},"assertion":[{"value":"2025-11-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e22929"}}