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Here, we aimed to characterize the association between retinal mononuclear phagocyte (MP) activation and retinal degeneration in the <jats:italic>RPE65\/rd12<\/jats:italic> mouse model of LCA.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Thirty-nine <jats:italic>RPE65\/rd12<\/jats:italic> and ten <jats:italic>C57BL\/6J<\/jats:italic> wild-type mice were used. <jats:italic>RPE65\/rd12<\/jats:italic> mice were treated with minocycline by daily intraperitoneal injection (5\u00a0mg\/kg) for eight weeks starting at age postnatal day 28 (P28). MP cell density in the subretina was determined by choroid-retinal pigment epithelium (RPE) flat mount analysis, and retinal function was determined by electroretinogram (ERG).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>In wild-type <jats:italic>C57BL\/6J<\/jats:italic> mice, MPs were exclusively located in the inner retinal layers at ages P28-P84. By contrast, in the <jats:italic>RPE65\/rd12<\/jats:italic> mice, MPs migrated into the subretina as early as P56 in a central-to-peripheral gradient. By P84, the density of MPs in the subretina increased by nearly 3-fold, reaching 61.3\u2009\u00b1\u20096.2 cell\/mm<jats:sup>2<\/jats:sup> and 33.1\u2009\u00b1\u20098 cell\/mm<jats:sup>2<\/jats:sup> in the central and peripheral retina, respectively. Minocycline treatment significantly reduced MP density in the peripheral subretina (16.2\u2009\u00b1\u20091.8 MP cell\/mm<jats:sup>2<\/jats:sup>) compared with mice treated with PBS (27.2\u2009\u00b1\u20092.4 MP cell\/mm<jats:sup>2<\/jats:sup>, respectively, <jats:italic>p<\/jats:italic>\u2009=\u20090.006). Maximal electroretinogram b-wave responses were significantly higher in minocycline- vs. PBS-treated mice under light-adapted conditions following eight weeks of treatment (mean\u2009\u00b1\u2009SE: 199\u00b5v\u2009\u00b1\u200928\u00b5v vs. 129.8\u00b5v\u2009\u00b1\u20099.8\u00b5v, <jats:italic>p<\/jats:italic>\u2009=\u20090.016).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Our data indicates that MP migration into the subretina is associated with retinal degeneration in<jats:italic> RPE65\/rd12<\/jats:italic> mice. Inhibiting MP migration into the subretina was associated with improved retinal function. These findings may guide the development of therapies targeting MP activation for neuroprotection in LCA and potentially other retinoid cycle-related retinal degeneration blinding diseases.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s00417-025-06768-y","type":"journal-article","created":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T21:16:52Z","timestamp":1750195012000},"page":"2485-2494","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Minocycline treatment reduces the activation of mononuclear phagocytes and improves retinal function in a mouse model of Leber congenital amaurosis"],"prefix":"10.1007","volume":"263","author":[{"given":"Ettel","family":"Bubis","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0859-6606","authenticated-orcid":false,"given":"Ifat","family":"Sher","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hadas","family":"Ketter-Katz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Estela","family":"Derzane","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4412-1341","authenticated-orcid":false,"given":"Florian","family":"Sennlaub","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2366-1779","authenticated-orcid":false,"given":"Ygal","family":"Rotenstreich","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,6,18]]},"reference":[{"key":"6768_CR1","doi-asserted-by":"publisher","first-page":"1795","DOI":"10.1016\/S0140-6736(06)69740-7","volume":"368","author":"DT Hartong","year":"2006","unstructured":"Hartong DT, Berson EL, Dryja TP (2006) Retinitis pigmentosa. 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