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Previous work showed that intravitreal (IVT) injection of iron induces acute photoreceptor death, lipid peroxidation, and autofluorescence (AF). Herein, we extend this work, finding surprising chronic features of the model: geographic atrophy and sympathetic ophthalmia. We provide new mechanistic insights derived from focal AF in the photoreceptors, quantification of bisretinoids, and localization of carboxyethyl pyrrole, an oxidized adduct of docosahexaenoic acid associated with AMD. In mice given IVT ferric ammonium citrate (FAC), RPE died in patches that slowly expanded at their borders, like human geographic atrophy. There was green AF in the photoreceptor ellipsoid, a mitochondria\u2010rich region, 4\u00a0h after injection, followed later by gold AF in rod outer segments, RPE and subretinal myeloid cells. The green AF signature is consistent with flavin adenine dinucleotide, while measured increases in the bisretinoid all\u2010<jats:italic>trans<\/jats:italic>\u2010retinal dimer are consistent with the gold AF. FAC induced formation carboxyethyl pyrrole accumulation first in photoreceptors, then in RPE and myeloid cells. Quantitative PCR on neural retina and RPE indicated antioxidant upregulation and inflammation. Unexpectedly, reminiscent of sympathetic ophthalmia, autofluorescent myeloid cells containing abundant iron infiltrated the saline\u2010injected fellow eyes only if the contralateral eye had received IVT FAC. These findings provide mechanistic insights into the potential toxicity caused by AMD\u2010associated retinal iron accumulation. The mouse model will be useful for testing antioxidants, iron chelators, ferroptosis inhibitors, anti\u2010inflammatory medications, and choroidal neovascularization inhibitors.<\/jats:p>","DOI":"10.1111\/acel.13490","type":"journal-article","created":{"date-parts":[[2021,10,10]],"date-time":"2021-10-10T14:41:34Z","timestamp":1633876894000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Intraocular iron injection induces oxidative stress followed by elements of geographic atrophy and sympathetic ophthalmia"],"prefix":"10.1111","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6652-5358","authenticated-orcid":false,"given":"Yingrui","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Ophthalmology The Second Hospital of Jilin University Changchun China"},{"name":"F.M. Kirby Center for Molecular Ophthalmology Scheie Eye Institute Perelman School of Medicine at the University of Pennsylvania Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brent A.","family":"Bell","sequence":"additional","affiliation":[{"name":"F.M. Kirby Center for Molecular Ophthalmology Scheie Eye Institute Perelman School of Medicine at the University of Pennsylvania Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Song","sequence":"additional","affiliation":[{"name":"F.M. Kirby Center for Molecular Ophthalmology Scheie Eye Institute Perelman School of Medicine at the University of Pennsylvania Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye J.","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Harkness Eye Institute Columbia University Medical Center New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob K.","family":"Sterling","sequence":"additional","affiliation":[{"name":"F.M. Kirby Center for Molecular Ophthalmology Scheie Eye Institute Perelman School of Medicine at the University of Pennsylvania Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin J.","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Scheie Eye Institute University of Pennsylvania Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maura","family":"Poli","sequence":"additional","affiliation":[{"name":"Department of Molecular and Translational Medicine University of Brescia Brescia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Guo","sequence":"additional","affiliation":[{"name":"F.M. Kirby Center for Molecular Ophthalmology Scheie Eye Institute Perelman School of Medicine at the University of Pennsylvania Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Zhang","sequence":"additional","affiliation":[{"name":"F.M. Kirby Center for Molecular Ophthalmology Scheie Eye Institute Perelman School of Medicine at the University of Pennsylvania Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aditya","family":"Rao","sequence":"additional","affiliation":[{"name":"Department of Molecular Life Science University of Pennsylvania Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet R.","family":"Sparrow","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Harkness Eye Institute Columbia University Medical Center New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanfang","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology The Second Hospital of Jilin University Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua L.","family":"Dunaief","sequence":"additional","affiliation":[{"name":"F.M. Kirby Center for Molecular Ophthalmology Scheie Eye Institute Perelman School of Medicine at the University of Pennsylvania Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,10,9]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3109\/02713688408997203"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.15-17026"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2015.05.019"},{"issue":"7","key":"e_1_2_10_5_1","first-page":"1830","article-title":"Molecular characterization of retinal pigment epithelium (RPE) correlating to hyperreflective foci (HRF) in age\u2010related macular degeneration (AMD)","volume":"61","author":"Cao D.","year":"2020","journal-title":"Investigative Ophthalmology & Visual Science"},{"issue":"2","key":"e_1_2_10_6_1","first-page":"496","article-title":"Autofluorescence distribution associated with drusen in age\u2010related macular degeneration","volume":"41","author":"Delori F. 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