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Despite evidence implicating mitochondrial dysfunction in glaucoma, the mechanisms linking elevated intraocular pressure, synaptic dysfunction, mitochondrial failure, and RGC death remain incompletely understood. Here we identify the mitochondrial scaffold protein A\u2010kinase anchoring protein 1 (AKAP1) as a critical regulator of RGC resilience in glaucoma. AKAP1 expression is reduced in glaucomatous retinas and correlates with disrupted mitochondrial dynamics, oxidative stress, synaptic impairment, and visual decline. AAV2\u2010mediated restoration of AKAP1 preserves RGC survival and visual function in two independent experimental glaucoma models. These data suggest that retinal AKAP1 promotes mitochondrial fusion, cristae integrity, and bioenergetic capacity in the inner retina and in stressed cultured RGCs, and is accompanied by increased mitochondrial content in presynaptic terminals of the inner plexiform layer. Retinal AKAP1 is further associated with higher PKA abundance, normalized CaMKII and synapsin phosphorylation, preserved synaptophysin, and lower complement C1q and glial activation markers; these associations do not, by themselves, establish causality. These findings identify AKAP1 as a candidate regulator of mitochondrial and synaptic homeostasis and highlight AAV2\u2010AKAP1 gene therapy as a promising neuroprotective strategy for vision preservation in glaucoma.<\/jats:p>","DOI":"10.1002\/advs.78349","type":"journal-article","created":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T15:04:21Z","timestamp":1792335861000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["AKAP1 Protects Retinal Ganglion Cells and Preserves Vision by Improving Mitochondrial and Synaptic Health in Glaucomatous Neurodegeneration"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3779-7178","authenticated-orcid":false,"given":"Tonking","family":"Bastola","sequence":"first","affiliation":[{"name":"Viterbi Family Department of Ophthalmology Viterbi Family Vision Research Center Shiley Eye Institute University of California San Diego  La Jolla California 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