{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T15:35:20Z","timestamp":1791387320157,"version":"4.3.3"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2014,4,1]],"date-time":"2014-04-01T00:00:00Z","timestamp":1396310400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,4,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Many degenerative retinal diseases illustrate retinal inflammatory changes that include infiltration of microglia and macrophages into the subretinal space. In this study, we examined the role of chemokines in the Abca4\u2212\/\u2212Rdh8\u2212\/\u2212 mouse model of Stargardt disease and the Mertk\u2212\/\u2212 mouse model of retinitis pigmentosa. PCR array analysis of 84 chemokines and related molecules revealed 84.6-fold elevated expression of Ccl3 (MIP-1a) 24 h after light exposure in Abca4\u2212\/\u2212Rdh8\u2212\/\u2212 mice. Only MIP-1 chemokines, including Ccl3 and Ccl4, displayed peak expression 24 h after light exposure, and peaked earlier than the other chemokines. Secretion of Ccl3 was documented only in microglia, whereas both microglia and retinal pigment epithelium cells produced Ccl2. Exposure of Cx3Cr1gfp\/\u0394Abca4\u2212\/\u2212Rdh8\u2212\/\u2212 mice to intense light resulted in the appearance of Cx3Cr1GFP+ monocytes in the subretinal space. To address the in vivo role of CCL3 in retinal degeneration, Ccl3\u2212\/\u2212Abca4\u2212\/\u2212Rdh8\u2212\/\u2212 mice and Ccl3\u2212\/\u2212Mertk\u2212\/\u2212 mice were generated. Following intense light exposure, Ccl3\u2212\/\u2212Abca4\u2212\/\u2212Rdh8\u2212\/\u2212 mice displayed persistent retinal inflammation with appearance of Iba-1+ cells in the subretinal space, severe photoreceptor cell death, and increased Ccl4 expression compared with Abca4\u2212\/\u2212Rdh8\u2212\/\u2212 mice. In contrast, Ccl3\u2212\/\u2212Abca4\u2212\/\u2212Rdh8\u2212\/\u2212 mice exhibited a milder retinal inflammation and degeneration than Abca4\u2212\/\u2212Rdh8\u2212\/\u2212 mice did in age-related chronic retinal degeneration under room light conditions. The deficiency of Ccl3 also attenuated the severity of retinal degeneration in Mertk\u2212\/\u2212 mice. Taken together, our results indicate that Ccl3 has an essential role in regulating the severity of retinal inflammation and degeneration in these mouse models.<\/jats:p>","DOI":"10.4049\/jimmunol.1301738","type":"journal-article","created":{"date-parts":[[2014,3,18]],"date-time":"2014-03-18T05:36:36Z","timestamp":1395120996000},"page":"3816-3827","source":"Crossref","is-referenced-by-count":78,"title":["CCL3 Production by Microglial Cells Modulates Disease Severity in Murine Models of Retinal Degeneration"],"prefix":"10.1093","volume":"192","author":[{"given":"Hideo","family":"Kohno","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Case Western Reserve University , Cleveland, OH 44106"},{"name":"Department of Ophthalmology, The Jikei University School of Medicine , Tokyo 105-8461,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadao","family":"Maeda","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Case Western Reserve University , Cleveland, OH 44106"},{"name":"Department of Ophthalmology and Visual Sciences, Case Western Reserve University , Cleveland, OH 44106"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsay","family":"Perusek","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, Case Western Reserve University , Cleveland, OH 44106"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Pearlman","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, Case Western Reserve University , Cleveland, OH 44106"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiko","family":"Maeda","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Case Western Reserve University , Cleveland, OH 44106"},{"name":"Department of Ophthalmology and Visual Sciences, Case Western Reserve University , Cleveland, OH 44106"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,4,15]]},"reference":[{"key":"2025032404244744300_r1","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1016\/j.preteyeres.2009.06.001","article-title":"Para-inflammation in the aging retina","volume":"28","author":"Xu","year":"2009","journal-title":"Prog. 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