{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T16:58:33Z","timestamp":1791392313479,"version":"4.3.3"},"reference-count":54,"publisher":"National Academy of Sciences","issue":"41","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,10,13]]},"abstract":"<jats:p>\n                    Retinal fibrosis is a blinding complication of proliferative diabetic retinopathy (PDR), proliferative vitreoretinopathy (PVR), age-related macular degeneration (AMD) and idiopathic epiretinal membrane (iERM), yet effective therapies remain lacking. The purpose of this study was to investigate the role of BMP2 and BMP4 (BMP2\/4)\u2013activin receptor-like kinase (ALK) signaling in retinal fibrosis. BMP2 was detected in the vitreous of PDR, PVR, and rhegmatogenous retinal detachment (RRD) samples at concentration of 70, 180, and 85 pg\/mL respectively, whereas it was present only at trace levels or was undetectable in the vitreous of macular hole and idiopathic ERM samples (~0.1 pg\/mL). PDR, PVR, and idiopathic ERMs exhibited strong immunoreactivity for BMP2, BMP4, ALK3 (Bmpr1a), pSMAD1\/5\/9, and pSMAD4. Formation of preretinal fibronectin-containing membranes resulted from intravitreal injection of wild-type mice with BMP2 and similar membranes formed in mice expressing constitutively active ALK3 (caBmpr1a). The presence of preretinal membrane in\n                    <jats:italic toggle=\"yes\">caBmpr1a<\/jats:italic>\n                    was confirmed by optical coherence tomography. The limited hyperoxia-induced proliferative retinopathy (LIHPR) model demonstrated a progressive increase in the retinal expression of BMP2 and BMP4and development of preretinal membrane. Administration of BMP\/ALK inhibitor LDN193189 induced regression of the preretinal membrane in LHIPR. BMP2 and BMP4 induced a significant increase in the expression of Glial Fibrillary Acidic Protein (GFAP), fibronectin, and collagen-VI in cultured rat Muller glial cells, and increased fibronectin was reversed by BMP\/ALK inhibition. BMP2 also significantly upregulated fibronectin and activated matrix metalloproteinase-2 in human retinal endothelial cells. These findings support BMP2\/4\u2013ALK signaling as a potential mediator and therapeutic target in retinal fibrosis.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2603111123","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T16:35:51Z","timestamp":1791390951000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":0,"title":["Bone morphogenetic protein signaling as a key regulator of retinal fibrosis"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-1009-3844","authenticated-orcid":false,"given":"Sonali","family":"Sharma","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01ythxj32","id-type":"ROR","asserted-by":"publisher"}],"name":"Eye Research Centre, Oakland University William Beaumont School of Medicine","place":["Rochester"]},{"id":[{"id":"https:\/\/ror.org\/01ythxj32","id-type":"ROR","asserted-by":"publisher"}],"name":"Eye Research 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