{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T22:37:43Z","timestamp":1790721463252,"version":"4.1.0"},"reference-count":38,"publisher":"National Academy of Sciences","issue":"26","license":[{"start":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T00:00:00Z","timestamp":1782432000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007013","name":"F. Hoffmann-La Roche","doi-asserted-by":"crossref","award":["Immunolgy incubator programme"],"award-info":[{"award-number":["Immunolgy incubator programme"]}],"id":[{"id":"10.13039\/100007013","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001602","name":"Science Foundation Ireland","doi-asserted-by":"publisher","award":["SFI 21\/SPP\/3732"],"award-info":[{"award-number":["SFI 21\/SPP\/3732"]}],"id":[{"id":"10.13039\/501100001602","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006312","name":"BrightFocus Foundation","doi-asserted-by":"publisher","award":["M2023011"],"award-info":[{"award-number":["M2023011"]}],"id":[{"id":"10.13039\/100006312","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,6,30]]},"abstract":"<jats:p>\n                    Fibrosis is the end-stage of a maladaptive process that occurs when the body\u2019s normal wound-healing strategy becomes dysregulated. Subretinal fibrosis is the end stage of neovascular age-related macular degeneration (nAMD), the most common cause of central vision loss in people over the age of 50. The cellular sources of excess extracellular matrix (ECM) contributing to subretinal fibrosis are unknown, as is the heterogeneity of cells involved in the fibrotic process. Here we identify cells contributing to subretinal fibrosis by using\n                    <jats:italic toggle=\"yes\">Col1a1<\/jats:italic>\n                    -YFP reporter mice to noninvasively image collagen production in real-time in vivo in two disease models, 1) a resolving retinal injury model and 2) a fibrotic model of subretinal disease. We create a collagen-producing eye cell atlas for subretinal injury and demonstrate subretinal fibroblast heterogeneity in healthy, resolving, and fibrotic tissue. We identify distinct molecular characteristics of general repair\/resolving fibroblast populations versus pathogenic pro-fibrotic collagen-producing fibroblasts. Integration of this collagen-producing eye cell atlas with a published collagen-producing lung cell atlas shows conserved pro-fibrotic fibroblasts in both organs, yet also uncovers tissue-specific fibroblast populations unique to subretinal fibrosis. A\n                    <jats:italic toggle=\"yes\">\n                      Fap\n                      <jats:sup>+<\/jats:sup>\n                      Fgl2\n                      <jats:sup>+<\/jats:sup>\n                    <\/jats:italic>\n                    fibroblast population significantly expands in subretinal fibrosis that expresses the highest levels of collagens and distinctively expresses ECM components\n                    <jats:italic toggle=\"yes\">Periostin<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">Col15a1<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">Col6a5<\/jats:italic>\n                    . Immunolabeling of mouse and human-donor eye tissue support the fibroblastic expression and perivascular location of periostin as clearly distinguishing between bona fide fibrosis and early disease in nAMD. Our collagen-producing eye cell atlas is a valuable resource for studying distinct fibroblast subsets in homeostasis, early injury, and fibrosis.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2519056123","type":"journal-article","created":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T17:38:56Z","timestamp":1782495536000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":2,"title":["Collagen-producing eye cell atlas reveals distinct fibroblast fates in early injury vs. fibrotic subretinal disease"],"prefix":"10.1073","volume":"123","author":[{"given":"Ema","family":"Ozaki","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02tyrky19","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Clinical Medicine, School of Medicine, Trinity College Dublin","place":["Dublin 2, Ireland"]},{"id":[{"id":"https:\/\/ror.org\/02tyrky19","id-type":"ROR","asserted-by":"publisher"}],"name":"Trinity College Institute of Neuroscience, Trinity College Dublin","place":["Dublin 2, Ireland"]},{"name":"Roche Pharma Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd.","place":["Basel, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2396-3750","authenticated-orcid":false,"given":"Said","family":"Aktas","sequence":"additional","affiliation":[{"name":"Pharma Research and Early Development, Roche Innovation Center Zurich, Roche Glycart AG.","place":["Schlieren, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly","family":"Mulfaul","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/036jqmy94","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Neuroscience and Pharmacology, University of Iowa","place":["Iowa City"]},{"id":[{"id":"https:\/\/ror.org\/036jqmy94","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute for Vision Research, University of Iowa","place":["Iowa City"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiva","family":"Brennan","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02tyrky19","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Clinical Medicine, School of Medicine, Trinity College Dublin","place":["Dublin 2, Ireland"]},{"id":[{"id":"https:\/\/ror.org\/02tyrky19","id-type":"ROR","asserted-by":"publisher"}],"name":"Trinity College Institute of Neuroscience, Trinity College Dublin","place":["Dublin 2, Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Roubeix","sequence":"additional","affiliation":[{"name":"Roche Pharma Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd.","place":["Basel, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Palko","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02tyrky19","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Clinical Medicine, School of Medicine, Trinity College Dublin","place":["Dublin 2, Ireland"]},{"id":[{"id":"https:\/\/ror.org\/02tyrky19","id-type":"ROR","asserted-by":"publisher"}],"name":"Trinity College Institute of Neuroscience, Trinity College Dublin","place":["Dublin 2, Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie","family":"Robb","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02tyrky19","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Clinical Medicine, School of Medicine, Trinity College Dublin","place":["Dublin 2, Ireland"]},{"id":[{"id":"https:\/\/ror.org\/02tyrky19","id-type":"ROR","asserted-by":"publisher"}],"name":"Trinity College Institute of Neuroscience, Trinity College Dublin","place":["Dublin 2, Ireland"]},{"name":"Progressive Vision Research","place":["Dublin 18, Ireland"]},{"id":[{"id":"https:\/\/ror.org\/03z0mke78","id-type":"ROR","asserted-by":"publisher"}],"name":"The Royal Victoria Eye and Ear Hospital","place":["Dublin 2, Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tai-Hsien","family":"Ou Yang","sequence":"additional","affiliation":[{"name":"Roche Pharma Research and Early Development, Data and Analytics, Roche Translational & Clinical Research Center, F. Hoffmann-La Roche Ltd.","place":["Little Falls"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3026-8932","authenticated-orcid":false,"given":"Marie-Claire","family":"Schanne-Klein","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/042tfbd02","id-type":"ROR","asserted-by":"publisher"}],"name":"Laboratoire d\u2019Optique et Biosciences, Ecole Polytechnique, CNRS, INSERM, Institut Polytechnique de Paris","place":["Palaiseau, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Toidze","sequence":"additional","affiliation":[{"name":"Roche Pharma Research and Early Development, Roche Innovation Center Basel, F. 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E. Dorrier . CNS fibroblasts form a fibrotic scar in response to immune cell infiltration. Nat. Neurosci. 24 234\u2013244 (2021) 10.1038\/s41593-020-00770-9.","DOI":"10.1038\/s41593-020-00770-9"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202400938"},{"key":"e_1_3_4_38_2","unstructured":"E. Ozaki Collagen-producing eye cell atlas reveals distinct fibroblast fates in early injury versus fibrotic subretinal disease. NCBI\u2018s Gene Expression Omnibus. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE318755. Deposited 6 February 2026."}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2519056123","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T17:39:13Z","timestamp":1782495553000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2519056123"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,26]]},"references-count":38,"journal-issue":{"issue":"26","published-print":{"date-parts":[[2026,6,30]]}},"alternative-id":["10.1073\/pnas.2519056123"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2519056123","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,26]]},"assertion":[{"value":"2025-07-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-02","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-26","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2519056123"}}