{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T21:54:30Z","timestamp":1791064470887,"version":"4.1.0"},"reference-count":55,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2013,8]]},"abstract":"<jats:sec>\n            <jats:title>Objective\u2014<\/jats:title>\n            <jats:p>Proinflammatory cytokines contribute to the development of retinal vasculopathies. However, the role of these factors and the mechanisms by which they elicit their effects in retina are not known. We investigated whether activated microglia during early stages of ischemic retinopathy produces excessive interleukin-1\u03b2 (IL-1\u03b2), which elicits retinal microvascular degeneration not directly but rather by triggering the release of the proapoptotic\/repulsive factor semaphorin-3A (Sema3A) from neurons.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results\u2014<\/jats:title>\n            <jats:p>\n              Sprague Dawley rats subjected to retinopathy induced by hyperoxia (80% O\n              <jats:sub>2<\/jats:sub>\n              ; O\n              <jats:sub>2<\/jats:sub>\n              -induced retinopathy) exhibited retinal vaso-obliteration associated with microglial activation, NLRP3 upregulation, and IL-1\u03b2 and Sema3A release; IL-1\u03b2 was mostly generated by microglia. Intraperitoneal administration of IL-1 receptor antagonists (Kineret, or rytvela [101.10]) decreased these effects and enhanced retinal revascularization; knockdown of Sema3A resulted in microvessel preservation and, conversely, administration of IL-1\u03b2 caused vaso-obliteration. In vitro, IL-1\u03b2 derived from activated primary microglial cells, cultured under hyperoxia, stimulated the release of Sema3A in retinal ganglion cells-5, which in turn induced apoptosis of microvascular endothelium; antagonism of IL-1 receptor decreased microglial activation and on retinal ganglion cells-5 abolished the release of Sema3A inhibiting ensuing endothelial cell apoptosis. IL-1\u03b2 was not directly cytotoxic to endothelial cells.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>\n              Our findings suggest that in the early stages of O\n              <jats:sub>2<\/jats:sub>\n              -induced retinopathy, retinal microglia are activated to produce IL-1\u03b2, which sustains the activation of microglia and induces microvascular injury through the release of Sema3A from adjacent neurons. Interference with IL-1 receptor or Sema3A actions preserves the microvascular bed in ischemic retinopathies and, consequently, decreases ensued pathological preretinal neovascularization.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.113.301331","type":"journal-article","created":{"date-parts":[[2013,6,14]],"date-time":"2013-06-14T06:02:17Z","timestamp":1371189737000},"page":"1881-1891","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":137,"title":["Microglia and Interleukin-1\u03b2 in Ischemic Retinopathy Elicit Microvascular Degeneration Through Neuronal Semaphorin-3A"],"prefix":"10.1161","volume":"33","author":[{"given":"Jos\u00e9 Carlos","family":"Rivera","sequence":"first","affiliation":[{"name":"From the Department of Pediatrics, Ophthalmology, and Pharmacology, CHU Sainte-Justine Research Center (J.C.R., B.N., D.H., A.M., J.-C.H., C.Q., J.-S.J., P.H., S.C.), Department of Ophthalmology, Maisonneuve-Rosemont Hospital Research Center (J.C.R., N.S., T.Z., S.C.), and Department of Chemistry (W.L.), Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, Qu\u00e9bec, Canada; and INSERM, UMR S 872, Paris, France (F.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Sitaras","sequence":"additional","affiliation":[{"name":"From the Department of Pediatrics, Ophthalmology, and Pharmacology, CHU Sainte-Justine Research Center (J.C.R., B.N., D.H., A.M., J.-C.H., C.Q., J.-S.J., P.H., S.C.), Department of Ophthalmology, Maisonneuve-Rosemont Hospital Research Center (J.C.R., N.S., T.Z., S.C.), and Department of Chemistry (W.L.), Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, Qu\u00e9bec, Canada; and INSERM, UMR S 872, Paris, France (F.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baraa","family":"Noueihed","sequence":"additional","affiliation":[{"name":"From the Department of Pediatrics, Ophthalmology, and Pharmacology, CHU Sainte-Justine Research Center (J.C.R., B.N., D.H., A.M., J.-C.H., C.Q., J.-S.J., P.H., S.C.), Department of Ophthalmology, Maisonneuve-Rosemont Hospital Research Center (J.C.R., N.S., T.Z., S.C.), and Department of Chemistry (W.L.), Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, Qu\u00e9bec, Canada; and INSERM, UMR S 872, Paris, France (F.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Hamel","sequence":"additional","affiliation":[{"name":"From the Department of Pediatrics, Ophthalmology, and Pharmacology, CHU Sainte-Justine Research Center (J.C.R., B.N., D.H., A.M., J.-C.H., C.Q., J.-S.J., P.H., S.C.), Department of Ophthalmology, Maisonneuve-Rosemont Hospital Research Center (J.C.R., N.S., T.Z., S.C.), and Department of Chemistry (W.L.), Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, Qu\u00e9bec, Canada; and INSERM, UMR S 872, Paris, France (F.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ankush","family":"Madaan","sequence":"additional","affiliation":[{"name":"From the Department of Pediatrics, Ophthalmology, and Pharmacology, CHU Sainte-Justine Research Center (J.C.R., B.N., D.H., A.M., J.-C.H., C.Q., J.-S.J., P.H., S.C.), Department of Ophthalmology, Maisonneuve-Rosemont Hospital Research Center (J.C.R., N.S., T.Z., S.C.), and Department of Chemistry (W.L.), Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, Qu\u00e9bec, Canada; 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