{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T18:06:22Z","timestamp":1791137182465,"version":"4.1.0"},"reference-count":38,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2023,6,30]],"date-time":"2023-06-30T00:00:00Z","timestamp":1688083200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Health\/National Eye Institute","award":["R01 EY027303"],"award-info":[{"award-number":["R01 EY027303"]}]},{"name":"National Institute of Health\/National Eye Institute","award":["R01 EY029269"],"award-info":[{"award-number":["R01 EY029269"]}]},{"name":"National Institute of Health\/National Eye Institute","award":["R01 EY032502"],"award-info":[{"award-number":["R01 EY032502"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Retinal detachment (RD) is a neurodegenerative blinding disease caused by plethora of clinical conditions. RD is characterized by the physical separation of retina from the underlying retinal pigment epithelium (RPE), eventually leading to photoreceptor cell death, inflammation, and vision loss. Albeit the activation of complement plays a critical role in the pathogenesis of RD, the retinal cellular source for complement production remains elusive. Here, using C3 tdTomato reporter mice we show that retinal injury upregulates C3 expression, specifically in M\u00fcller cells. Activation of the complement cascade results in the generation of proinflammatory cleaved products, C3a and C5a, that bind C3aR and C5aR1, respectively. Our flow cytometry data show that retinal injury significantly upregulated C3aR and C5aR1 in microglia and resulted in the infiltration of peripheral immune cells. Loss of C3, C5, C3aR or C5aR1 reduced photoreceptor cell death and infiltration of microglia and peripheral immune cells into the sub-retinal space. These results indicate that C3\/C3aR and C5\/C5aR1 play a crucial role in eliciting photoreceptor degeneration and inflammatory responses in RD.<\/jats:p>","DOI":"10.3390\/cells12131754","type":"journal-article","created":{"date-parts":[[2023,6,30]],"date-time":"2023-06-30T16:08:32Z","timestamp":1688141312000},"page":"1754","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Retinal Injury Activates Complement Expression in M\u00fcller Cells Leading to Neuroinflammation and Photoreceptor Cell Death"],"prefix":"10.3390","volume":"12","author":[{"given":"Steven J.","family":"Tabor","sequence":"first","affiliation":[{"name":"Angiogenesis Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kentaro","family":"Yuda","sequence":"additional","affiliation":[{"name":"Angiogenesis Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7529-1899","authenticated-orcid":false,"given":"Jonathan","family":"Deck","sequence":"additional","affiliation":[{"name":"Tulane University School of Medicine, Tulane Medical Center, New Orleans, LA 70112, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gopalan","family":"Gnanaguru","sequence":"additional","affiliation":[{"name":"Angiogenesis Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2048-9080","authenticated-orcid":false,"given":"Kip M.","family":"Connor","sequence":"additional","affiliation":[{"name":"Angiogenesis Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/S0039-6257(05)80092-X","article-title":"An international classification and grading system for age-related maculopathy and age-related macular degeneration. 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