{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T12:05:17Z","timestamp":1790683517006,"version":"4.1.0"},"reference-count":70,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2020,7,27]],"date-time":"2020-07-27T00:00:00Z","timestamp":1595808000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["R01EY025641"],"award-info":[{"award-number":["R01EY025641"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006312","name":"BrightFocus Foundation","doi-asserted-by":"publisher","award":["M2019069"],"award-info":[{"award-number":["M2019069"]}],"id":[{"id":"10.13039\/100006312","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Ferrochelatase\u00a0(FECH) is the terminal enzyme\u00a0in heme biosynthesis. We previously showed that FECH is required for endothelial cell growth in vitro and choroidal neovascularization in vivo. But FECH has not been explored in retinal neovascularization, which underlies diseases like proliferative diabetic retinopathy and retinopathy of prematurity. Here, we investigated the inhibition of FECH using genetic and chemical approaches in the oxygen\u2010induced retinopathy (OIR) mouse model. In OIR mice, FECH expression is upregulated and co\u2010localized with neovascular tufts. Partial loss\u2010of\u2010function\n                    <jats:italic>Fech<\/jats:italic>\n                    <jats:sup>m1Pas<\/jats:sup>\n                    \u00a0mutant mice showed reduced retinal neovascularization and endothelial cell proliferation in OIR. An intravitreal injection of the FECH inhibitor\n                    <jats:italic>N<\/jats:italic>\n                    \u2010methyl protoporphyrin had similar effects. Griseofulvin is an antifungal drug that inhibits FECH as an off\u2010target effect. Strikingly, intravitreal griseofulvin decreased both pathological tuft formation and areas of vasoobliteration compared to vehicle, suggesting potential as a FECH\u2010targeting therapy. Ocular toxicity studies revealed that intravitreal injection of griseofulvin in adult mice does not disrupt retinal vasculature, function, or morphology. In sum, mutation and chemical inhibition of\n                    <jats:italic>Fech<\/jats:italic>\n                    reduces retinal neovascularization and promotes physiological angiogenesis, suggesting a dual effect on vascular repair upon FECH inhibition, without ocular toxicity. These findings suggest that FECH inhibitors could be repurposed to treat retinal neovascularization.\n                  <\/jats:p>","DOI":"10.1096\/fj.202000964r","type":"journal-article","created":{"date-parts":[[2020,7,27]],"date-time":"2020-07-27T09:10:05Z","timestamp":1595841005000},"page":"12419-12435","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Ferrochelatase regulates retinal neovascularization"],"prefix":"10.1096","volume":"34","author":[{"given":"Sardar Pasha Sheik","family":"Pran Babu","sequence":"first","affiliation":[{"name":"Eugene and Marilyn Glick Eye Institute Indiana University School of Medicine Indianapolis IN USA"},{"name":"Department of Ophthalmology Indiana University School of Medicine Indianapolis IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darcy","family":"White","sequence":"additional","affiliation":[{"name":"Eugene and Marilyn Glick Eye Institute Indiana University School of Medicine Indianapolis IN USA"},{"name":"Department of Ophthalmology Indiana University School of Medicine Indianapolis IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy W.","family":"Corson","sequence":"additional","affiliation":[{"name":"Eugene and Marilyn Glick Eye Institute Indiana University School of Medicine Indianapolis IN USA"},{"name":"Department of Ophthalmology Indiana University School of Medicine Indianapolis IN USA"},{"name":"Department of Biochemistry and Molecular Biology Indiana University School of Medicine Indianapolis IN USA"},{"name":"Department of Pharmacology and Toxicology Indiana University School of Medicine Indianapolis IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,7,27]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-4652(200009)184:3<301::AID-JCP3>3.0.CO;2-H"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2015.06.002"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI42142"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00005.2016"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.1947"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI44900"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-10-311589"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature04482"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/359843a0"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2008.05.001"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1167\/tvst.5.2.10"},{"key":"e_1_2_9_13_1","first-page":"145","article-title":"Anti\u2010VEGF for ROP and pediatric retinal diseases","volume":"7","author":"Wu AL","year":"2018","journal-title":"Asia Pac J Ophthalmol (Phila)"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.semperi.2019.05.011"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1208129"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaapos.2016.09.013"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2016.12.025"},{"key":"e_1_2_9_18_1","first-page":"CD009734","article-title":"Anti\u2010vascular endothelial growth factor (VEGF) drugs for treatment of retinopathy of prematurity","volume":"2","author":"Sankar MJ","year":"2016","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1039\/C4OB01604A"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.5b00449"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr9001116"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2012.04.009"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jcim.6b00216"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201606561"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep41975"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr400368e"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2015.09.002"},{"key":"e_1_2_9_28_1","first-page":"127","article-title":"Hepatic damage and oxidative stress induced by griseofulvin in mice","volume":"55","author":"Martinez MDC","year":"2009","journal-title":"Cell Mol Biol"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMe058142"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-cellbio-092910-154002"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.10-5176"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.03-0244"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.04-1361"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/0-387-32442-9_24"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.2741\/1056"},{"key":"e_1_2_9_36_1","first-page":"515","article-title":"Optical coherence tomography enables imaging of tumor initiation in the TAg\u2010RB mouse model of retinoblastoma","volume":"21","author":"Wenzel AA","year":"2015","journal-title":"Mol Vis"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115491"},{"key":"e_1_2_9_38_1","first-page":"101","article-title":"Oxygen\u2010induced retinopathy in the mouse","volume":"35","author":"Smith LE","year":"1994","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-61779-848-1_15"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep25509"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.visres.2004.03.011"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.visres.2004.05.018"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.118.248088"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1442-9071.2003.00664.x"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschembio.7b00854"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-09743-8"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1101\/pdb.prot073411"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.22846"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2009.187"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.2147\/EB.S94447"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0022244"},{"key":"e_1_2_9_52_1","first-page":"182","article-title":"Hypoxia inducible factor\u20101alpha is increased in ischemic retina: temporal and spatial correlation with VEGF expression","volume":"40","author":"Ozaki H","year":"1999","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2011.10.013"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20060753"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0200307"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-03-0773"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2004.03.027"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-4-19"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1993.1242"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2008.12.013"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1469-7580.2002.00064.x"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1346-8138.2007.00386.x"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2014.00061"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2013.091991"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2006.8.1153"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2012.00119"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1089\/152308603764816514"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-06-1974"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2018.06.009"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.01015"},{"key":"e_1_2_9_71_1","article-title":"Heme synthesis inhibition blocks angiogenesis via mitochondrial dysfunction","author":"Shetty T","journal-title":"iScience"}],"container-title":["The FASEB Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1096%2Ffj.202000964R","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.202000964R","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1096\/fj.202000964R","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.202000964R","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T21:20:03Z","timestamp":1761686403000},"score":1,"resource":{"primary":{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/10.1096\/fj.202000964R"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,27]]},"references-count":70,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2020,9]]}},"alternative-id":["10.1096\/fj.202000964R"],"URL":"https:\/\/doi.org\/10.1096\/fj.202000964r","archive":["Portico"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.06.02.129650","asserted-by":"object"}]},"ISSN":["0892-6638","1530-6860"],"issn-type":[{"value":"0892-6638","type":"print"},{"value":"1530-6860","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,27]]},"assertion":[{"value":"2020-06-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-07-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-07-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}