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Retinal abnormalities are a hallmark of LOAD, and our recent study demonstrated significant age\u2010related retinal impairments in\n                    <jats:italic>APOE4<\/jats:italic>\n                    \u2010knock\u2010in (KI) mice, highlighting that retinal impairments occur before the onset of cognitive decline in these mice. M\u00fcller cells (MCs), key retinal glia, are vital for retinal health, and their dysfunction may contribute to retinal impairments seen in AD. MCs maintain potassium balance via specialized inwardly rectifying K\n                    <jats:sup>+<\/jats:sup>\n                    channels 4.1 (Kir4.1). This study posits that Kir4.1 channels will be impaired in\n                    <jats:italic>APOE4<\/jats:italic>\n                    \u2010KI, resulting in MC dysfunction. Additionally, we demonstrate that MC dysfunction in\n                    <jats:italic>APOE4<\/jats:italic>\n                    \u2010KI stems from alterations in mitochondrial dynamics and oxidative stress. Kir4.1 expression and function were studied using immunofluorescence and through the whole\u2010cell voltage clamp, respectively. In parallel, rat M\u00fcller cells (rMC\u20101) were used to create an in\u00a0vitro model for further mechanistic studies. MitoQ was used to evaluate its potential to mitigate\n                    <jats:italic>APOE4<\/jats:italic>\n                    \u2010induced deficits.\n                    <jats:italic>APOE4<\/jats:italic>\n                    retinas and\n                    <jats:italic>APOE4<\/jats:italic>\n                    \u2010transfected rMC\u20101 significantly reduced Kir4.1 expression, K+ buffering capacity, and increased mitochondrial damage.\n                    <jats:italic>APOE4<\/jats:italic>\n                    \u2010transfected rMC\u20101 showed reduced mitochondrial membrane potential (\u0394\u03a8m) and increased mitochondrial reactive oxygen species (ROS). MitoQ treatment significantly reduced mitochondrial ROS and restored Kir4.1 expression in\n                    <jats:italic>APOE4<\/jats:italic>\n                    \u2010expressing cells. Our results demonstrate that\n                    <jats:italic>APOE4<\/jats:italic>\n                    causes mitochondrial dysfunction and MC impairment, which may contribute to retinal pathology in AD. MitoQ restored mitochondrial health and Kir4.1 expression in\n                    <jats:italic>APOE4<\/jats:italic>\n                    \u2010expressing rMC\u20101, suggesting targeting mitochondria may offer a promising therapeutic strategy for AD.\n                  <\/jats:p>","DOI":"10.1002\/glia.70119","type":"journal-article","created":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T08:09:31Z","timestamp":1767859771000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["M\u00fcller Glial Kir4.1 Channel Dysfunction in\n                    <i>APOE4<\/i>\n                    \u2010\n                    <scp>KI<\/scp>\n                    Model of Alzheimer's Disease"],"prefix":"10.1002","volume":"74","author":[{"given":"Surabhi D.","family":"Abhyankar","sequence":"first","affiliation":[{"name":"Department of Ophthalmology Indiana University School of Medicine  Indianapolis Indiana USA"},{"name":"Department of Biochemistry and Molecular Biology Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yucheng","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Biology, School of Science Indiana University  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neha","family":"Mahajan","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianyi","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodore R.","family":"Cummins","sequence":"additional","affiliation":[{"name":"Department of Biology, School of Science Indiana University  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian L.","family":"Oblak","sequence":"additional","affiliation":[{"name":"Stark Neurosciences Research Institute  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce T.","family":"Lamb","sequence":"additional","affiliation":[{"name":"Stark Neurosciences Research Institute  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy W.","family":"Corson","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Indiana University School of Medicine  Indianapolis Indiana USA"},{"name":"Department of Biochemistry and Molecular Biology Indiana University School of Medicine  Indianapolis Indiana USA"},{"name":"Stark Neurosciences Research Institute  Indianapolis Indiana USA"},{"name":"Leslie Dan Faculty of Pharmacy University of Toronto  Toronto Ontario 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