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Mononuclear phagocytic cells (MPCs) are known to accumulate in the subretinal space, generating a chronic inflammatory state that promotes the growth of the choroidal neovasculature. However, how the MPCs are recruited and activated to promote CNV pathology is not fully understood. Using genetic and pharmacological tools in a mouse model of laser-induced CNV, we demonstrate a role for the p75 neurotrophin receptor (p75NTR) in the recruitment of MPCs, in glial activation, and in vascular alterations. After laser injury, expression of p75NTR is increased in activated Muller glial cells near the CNV area in the retina and the retinal pigmented epithelium (RPE)-choroid. In p75NTR knockout mice (p75NTR KO) with CNV, there is significantly reduced recruitment of MPCs, reduced glial activation, reduced CNV area, and the retinal function is preserved, as compared to wild type mice with CNV. Notably, a single intravitreal injection of a pharmacological p75NTR antagonist in wild type mice with CNV phenocopied the results of the p75NTR KO mice. Our results demonstrate that p75NTR is etiological in the development of CNV.<\/jats:p>","DOI":"10.3390\/cells12020297","type":"journal-article","created":{"date-parts":[[2023,1,12]],"date-time":"2023-01-12T05:45:33Z","timestamp":1673502333000},"page":"297","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Etiological Roles of p75NTR in a Mouse Model of Wet Age-Related Macular Degeneration"],"prefix":"10.3390","volume":"12","author":[{"given":"Paula Virginia","family":"Subirada","sequence":"first","affiliation":[{"name":"Instituto Ferreyra, INIMEC-CONICET-Universidad Nacional de C\u00f3rdoba, C\u00f3rdoba 5016, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albana","family":"Tovo","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica Cl\u00ednica, Centro de Investigaciones en Bioqu\u00edmica Cl\u00ednica e Inmunolog\u00eda (CIBICI-CONICET), Universidad Nacional de C\u00f3rdoba, C\u00f3rdoba 5016, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Victoria","family":"Vaglienti","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica Cl\u00ednica, Centro de Investigaciones en Bioqu\u00edmica Cl\u00ednica e Inmunolog\u00eda (CIBICI-CONICET), Universidad Nacional de C\u00f3rdoba, C\u00f3rdoba 5016, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4203-7667","authenticated-orcid":false,"given":"Jos\u00e9 Domingo","family":"Luna Pinto","sequence":"additional","affiliation":[{"name":"Centro Privado de Ojos Romagosa, Fundaci\u00f3n VER, C\u00f3rdoba 5000, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6884-8815","authenticated-orcid":false,"given":"Horacio Uri","family":"Saragovi","sequence":"additional","affiliation":[{"name":"Lady Davis Research Institute-Jewish General Hospital, Center for Experimental Therapeutics, Department of Pharmacology and Therapeutics, Department of Ophthalmology and Vision Sciences, McGill University, Montreal, QC H3T 1E2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4760-8518","authenticated-orcid":false,"given":"Maria Cecilia","family":"S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica Cl\u00ednica, Centro de Investigaciones en Bioqu\u00edmica Cl\u00ednica e Inmunolog\u00eda (CIBICI-CONICET), Universidad Nacional de C\u00f3rdoba, C\u00f3rdoba 5016, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7238-9041","authenticated-orcid":false,"given":"Agust\u00edn","family":"Anastas\u00eda","sequence":"additional","affiliation":[{"name":"Instituto Ferreyra, INIMEC-CONICET-Universidad Nacional de C\u00f3rdoba, C\u00f3rdoba 5016, Argentina"},{"name":"Instituto Universitario de Ciencias Biom\u00e9dicas de C\u00f3rdoba (IUCBC), C\u00f3rdoba 5016, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8248-2282","authenticated-orcid":false,"given":"Pablo Federico","family":"Barcelona","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica Cl\u00ednica, Centro de Investigaciones en Bioqu\u00edmica Cl\u00ednica e Inmunolog\u00eda (CIBICI-CONICET), Universidad Nacional de C\u00f3rdoba, C\u00f3rdoba 5016, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e106","DOI":"10.1016\/S2214-109X(13)70145-1","article-title":"Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: A systematic review and meta-analysis","volume":"2","author":"Wong","year":"2014","journal-title":"Lancet Glob. 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