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Astrocytes extensively express connexin 43 (Cx43), a protein that forms gap junction (GJ) channels and transmembrane unopposed hemichannels. While it is well documented that Cx43 expression is augmented in retinal injuries, the role of astrocytic Cx43 channels in glaucomatous injury is not fully understood. Here, we used a mouse model of ocular hypertension caused by intracameral microbead injections and a more severe model, optic nerve crush (ONC) injury, and assessed changes in Cx43 expression and GJ channel function. The effect of astrocyte\u2010specific deletion of Cx43 (Cx43KO) on retinal ganglion cell (RGC) loss and visual function was also assessed. We show that the Cx43 expression is increased in retinal astrocytes at early time points and remained elevated even after sustained elevation of intraocular pressure (IOP) (~8\u2009weeks), which paralleled an increase in astrocytic GJ coupling. Deletion of astrocytic Cx43 markedly improved the survival of RGCs by ~93% and preserved visual function as assessed by ERG and reduced numbers of activated microglial\/macrophages in the glaucomatous retina. Cx43 expression was also substantially increased after ONC injury, and the absence of Cx43 in this model increased RGC survival by ~48%. These results reveal a deleterious role for Cx43 in glaucoma progression. Intravitreal injections of Gap19, a peptide that reportedly inhibits Cx43 hemichannels but not GJ channels, markedly increased RGC survival and visual function. Further studies are required to assess whether targeting Cx43 hemichannels might be useful for glaucoma treatment.<\/jats:p>","DOI":"10.1002\/glia.70013","type":"journal-article","created":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T05:34:35Z","timestamp":1743399275000},"page":"1398-1419","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Targeting Connexin 43 in Retinal Astrocytes Promotes Neuronal Survival in Glaucomatous Injury"],"prefix":"10.1002","volume":"73","author":[{"given":"Khulan","family":"Batsuuri","sequence":"first","affiliation":[{"name":"Department of Biological and Vision Sciences SUNY College of Optometry  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3501-1418","authenticated-orcid":false,"given":"Abduqodir H.","family":"Toychiev","sequence":"additional","affiliation":[{"name":"Department of Biological and Vision Sciences SUNY College of Optometry  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3017-7339","authenticated-orcid":false,"given":"Suresh","family":"Viswanathan","sequence":"additional","affiliation":[{"name":"Indiana University School of Optometry  Bloomington Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2559-7678","authenticated-orcid":false,"given":"Stefanie G.","family":"Wohl","sequence":"additional","affiliation":[{"name":"Department of Biological and Vision Sciences SUNY College of Optometry  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7986-8472","authenticated-orcid":false,"given":"Miduturu","family":"Srinivas","sequence":"additional","affiliation":[{"name":"Department of Biological and Vision Sciences SUNY College of Optometry  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3,28]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2014.00306"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI91948"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.24074"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature17623"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.2147\/OPTH.S19453"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2011.07595.x"},{"key":"e_1_2_9_8_1","first-page":"1258","article-title":"Retinal Morphology and ERG Response in the DBA\/2NNia Mouse Model of Angle\u2010Closure Glaucoma","volume":"42","author":"Bayer A. 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