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Specifically, chronically activated microglia and their disturbed regulatory system contribute to retinal degeneration. Galectin-3, a \u03b2-galactose binding protein, is a potent driver of macrophage and microglia activation and has been implicated in neuroinflammation, including neurodegenerative diseases of the brain. Here, we hypothesized that genetic deficiency of galectin-3 or its modulation via TD139 dampens mononuclear phagocyte reactivity and delays retinal degeneration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Galectin-3 expression in AMD patients was analyzed by immunohistochemical stainings. Galectin-3 knockout and BALB\/cJ mice were exposed to white bright light with an intensity of 15,000\u00a0lux for 1\u00a0h and Cx3cr1\n                      <jats:sup>GFP\/+<\/jats:sup>\n                      mice to focal blue light of 50,000\u00a0lux for 10\u00a0min. BALB\/cJ and Cx3cr1\n                      <jats:sup>GFP\/+<\/jats:sup>\n                      mice received intraperitoneal injections of 15\u00a0mg\/kg TD139 or vehicle for five consecutive days, starting one day prior to light exposure. The effects of galectin-3 deficiency or inhibition on microglia were analyzed by immunohistochemical stainings and in situ hybridization of retinal sections and flat mounts. Pro-inflammatory cytokine levels in the retina and retinal pigment epithelium (RPE) were quantified by qRT-PCR and transcriptomic changes were analyzed by RNA-sequencing. Retinal thickness and structure were evaluated by optical coherence tomography.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We found that galectin-3 expression was strongly upregulated in reactive retinal mononuclear phagocytes of AMD patients and in the two related mouse models of light-induced retinal degeneration. The experimental in vivo data further showed that specific targeting of galectin-3 by genetic knockout or administration of the small-molecule inhibitor TD139 reduced microglia reactivity and delayed retinal damage in both light damage conditions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study defines galectin-3 as a potent driver of retinal degeneration and highlights the protein as a drug target for ocular immunomodulatory therapies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12974-022-02589-6","type":"journal-article","created":{"date-parts":[[2022,9,17]],"date-time":"2022-09-17T06:02:43Z","timestamp":1663394563000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Genetic targeting or pharmacological inhibition of galectin-3 dampens microglia reactivity and delays retinal degeneration"],"prefix":"10.1186","volume":"19","author":[{"given":"Mona","family":"Tabel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Wolf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manon","family":"Szczepan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heping","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herbert","family":"J\u00e4gle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Moehle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Langmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,9,17]]},"reference":[{"key":"2589_CR1","doi-asserted-by":"publisher","first-page":"716","DOI":"10.1136\/bjo.86.7.716","volume":"86","author":"I Kocur","year":"2002","unstructured":"Kocur I, Resnikoff S. 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J Med Chem. 2016;59(17):8141\u20137.","journal-title":"J Med Chem"}],"container-title":["Journal of Neuroinflammation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12974-022-02589-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12974-022-02589-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12974-022-02589-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,17]],"date-time":"2022-09-17T11:02:57Z","timestamp":1663412577000},"score":1,"resource":{"primary":{"URL":"https:\/\/jneuroinflammation.biomedcentral.com\/articles\/10.1186\/s12974-022-02589-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,17]]},"references-count":47,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["2589"],"URL":"https:\/\/doi.org\/10.1186\/s12974-022-02589-6","relation":{},"ISSN":["1742-2094"],"issn-type":[{"value":"1742-2094","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,17]]},"assertion":[{"value":"30 March 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 September 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 September 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All experiments with human tissues were performed in accordance with the tenets of the Declaration of Helsinki, with the Human Tissue Act (2004) and were approved by the local Ethical Review Boards of Queen\u2019s University Belfast. All animal experiments were reviewed and approved by the government office responsible for animal welfare in North-Rhine-Westphalia (Landesamt f\u00fcr Natur, Umwelt und Verbraucherschutz approval no. 81\u201302.04.2018.A303) and by the Animal Welfare and Ethical Review Board of Queen\u2019s University Belfast under the regulation of the UK Home Office Animal (Scientific Procedures) Act 1986.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing financial interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"229"}}