{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T05:23:27Z","timestamp":1787376207257,"version":"build-2736575974"},"reference-count":71,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100001818","name":"Research to Prevent Blindness","doi-asserted-by":"publisher","award":["Unrestricted award to the Department of Ophthalmology and Visual Sciences"],"award-info":[{"award-number":["Unrestricted award to the Department of Ophthalmology and Visual Sciences"]}],"id":[{"id":"10.13039\/100001818","id-type":"DOI","asserted-by":"publisher"}]},{"award":["Unrestricted award to the Department of Ophthalmology and Visual Sciences"],"award-info":[{"award-number":["Unrestricted award to the Department of Ophthalmology and Visual Sciences"]}],"id":[{"id":"https:\/\/ror.org\/04drjs621","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013779","name":"Retina Research Foundation","doi-asserted-by":"publisher","award":["Endoument Funds"],"award-info":[{"award-number":["Endoument Funds"]}],"id":[{"id":"10.13039\/100013779","id-type":"DOI","asserted-by":"publisher"}]},{"award":["Endoument Funds"],"award-info":[{"award-number":["Endoument Funds"]}],"id":[{"id":"https:\/\/ror.org\/05n2ytn05","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Edward N. &amp; Della L. 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J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Ocular diseases, such as neovascular age-related macular degeneration (nAMD) and proliferative vitreoretinopathy (PVR), have a fibrotic component that negatively impacts vision. Unfortunately, few treatments are available to mitigate fibrosis in the eye. The clearance of inflammatory cells proceeds, at least in part, through the intrinsic cell death pathway in which Bcl-2 family members play integral roles. Here, we assessed the influence of Bcl-2 expression in mononuclear phagocytes (MP) on the engagement and clearance of inflammatory cells, choroidal neovascularization (CNV), and subsequent subretinal fibrosis in a mouse laser-induced CNV model. Lack of Bcl-2 expression in MP (Bcl-2MP mice) decreased neutrophil (Gr1+) and microglia (Iba1+) presence without impacting M1 (CD80+) and M2 (CD206+) macrophage presence, CNV, or fibrosis during the first 2 weeks following laser photocoagulation. Later, after inflammation dampens, decreased later-stage fibrosis and CNV were noted in Bcl-2MP mice, which were accompanied by increased presence of M2 macrophages (CD206+). However, how these increased levels of CD206+ M2 macrophages in the absence of Bcl-2 contribute to decreased CNV and fibrosis remains unknown. To address whether Bcl-2 expression affects other forms of ocular fibrosis, we utilized the dispase PVR model. Bcl-2MP mice, or treatment of wild-type mice with Bcl-2 inhibitors, significantly decreased fibrosis in the PVR model. Furthermore, Bcl-2 inhibitors mitigated CNV and fibrosis (collagen I-defined) in wild-type mice during laser photocoagulation. Thus, inhibition of Bcl-2 activity prevents the late-stage clearance of CD206+ M2 macrophages during nAMD and PVR, mitigating ocular neovascularization and fibrosis.<\/jats:p>","DOI":"10.3390\/ijms27167455","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T12:57:53Z","timestamp":1787230673000},"page":"7455","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Bcl-2-Dependent Persistence of Mononuclear Phagocytes Promotes Ocular Fibrosis"],"prefix":"10.3390","volume":"27","author":[{"given":"Yong-Seok","family":"Song","sequence":"first","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA"},{"name":"McPherson Eye Research Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shoujian","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA"},{"name":"McPherson Eye Research Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soesiawati R.","family":"Darjatmoko","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA"},{"name":"McPherson Eye Research Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2723-9217","authenticated-orcid":false,"given":"Nader","family":"Sheibani","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA"},{"name":"McPherson Eye Research Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA"},{"name":"Department of Cell and Regenerative Biology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine M.","family":"Sorenson","sequence":"additional","affiliation":[{"name":"McPherson Eye Research Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA"},{"name":"Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2606","DOI":"10.1056\/NEJMra0801537","article-title":"Age-related macular degeneration","volume":"358","author":"Jager","year":"2008","journal-title":"N. 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