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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2024,12,24]]},"abstract":"<jats:p>Tissue inflammation is often broadly associated with cellular damage, yet sterile inflammation also plays critical roles in beneficial tissue remodeling. In the central nervous system, this is observed through a predominantly innate immune response in retinal vascular diseases such as age-related macular degeneration, diabetic retinopathy, and retinopathy of prematurity. Here, we set out to elucidate the dynamics of the immune response during progression and regression of pathological neovascularization in retinopathy. In a mouse model of oxygen-induced retinopathy, we report that dexamethasone, a broad-spectrum corticosteroid, suppresses initial formation of pathological preretinal neovascularization in early stages of disease, yet blunts reparative inflammation by impairing distinct myeloid cell populations, and hence reduces beneficial vascular remodeling in later stages of disease. Using genetic depletion of distinct components of the innate immune response, we demonstrate that CX3C chemokine receptor 1-expressing microglia contribute to angiogenesis. Conversely, myeloid cells expressing lysozyme 2 are recruited to sites of damaged blood vessels and pathological neovascularization where they partake in a reparative process that ultimately restores circulatory homeostasis to the retina. Hence, the Janus-faced properties of anti-inflammatory drugs should be considered, particularly in stages associated with persistent neovascularization.<\/jats:p>","DOI":"10.1073\/pnas.2411640121","type":"journal-article","created":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T13:38:39Z","timestamp":1734529119000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":17,"title":["Corticosteroids reduce pathological angiogenesis yet compromise reparative vascular remodeling in a model of retinopathy"],"prefix":"10.1073","volume":"121","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5248-5762","authenticated-orcid":false,"given":"Masayuki","family":"Hata","sequence":"first","affiliation":[{"name":"Departments of Ophthalmology, Maisonneuve-Rosemont Hospital Research Centre, University of Montreal","place":["Montreal, Canada"]},{"name":"Department of Biochemistry and Molecular Medicine, Maisonneuve-Rosemont Hospital Research 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Research Center","place":["Montr\u00e9al, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9664-3518","authenticated-orcid":false,"given":"Gael","family":"Cagnone","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics, Ophthalmology, and Pharmacology, Centre Hospitalier, Universitaire Ste-Justine Research Center","place":["Montr\u00e9al, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yotaro","family":"Ochi","sequence":"additional","affiliation":[{"name":"Department of Pathology and Tumour Biology, Graduate School of Medicine, Kyoto University","place":["Kyoto, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Crespo-Garcia","sequence":"additional","affiliation":[{"name":"Departments of Ophthalmology, Maisonneuve-Rosemont Hospital Research Centre, University of Montreal","place":["Montreal, Canada"]},{"name":"Department of Biochemistry and 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