{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T17:14:32Z","timestamp":1790010872353,"version":"4.0.1"},"reference-count":43,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2019,6,25]],"date-time":"2019-06-25T00:00:00Z","timestamp":1561420800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["EY019949; EY025061"],"award-info":[{"award-number":["EY019949; EY025061"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001818","name":"Research to Prevent Blindness","doi-asserted-by":"publisher","award":["an Unrestricted Grant to the Department of Ophthalmology, SUNY-Buffalo"],"award-info":[{"award-number":["an Unrestricted Grant to the Department of Ophthalmology, SUNY-Buffalo"]}],"id":[{"id":"10.13039\/100001818","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Retinal neuronal injury and degeneration is one of the primary manifestations of diabetic retinopathy, a leading cause of vision loss in working age adults. In pathological conditions, including diabetes and some physiological conditions such as aging, protein homeostasis can become disrupted, leading to endoplasmic reticulum (ER) stress. Severe or unmitigated ER stress can lead to cell death, which in retinal neurons results in irreversible loss of visual function. X-box binding protein 1 (XBP1) is a major transcription factor responsible for the adaptive unfolded protein response (UPR) to maintain protein homeostasis in cells undergoing ER stress. The purpose of this study is to determine the role of XBP1-mediated UPR in retinal neuronal survival and function in a mouse model of type 1 diabetes. Using a conditional retina-specific XBP1 knockout mouse line, we demonstrate that depletion of XBP1 in retinal neurons results in early onset retinal function decline, loss of retinal ganglion cells and photoreceptors, disrupted photoreceptor ribbon synapses, and M\u00fcller cell activation after induction of diabetes. Our findings suggest an important role of XBP1-mediated adaptive UPR in retinal neuronal survival and function in diabetes.<\/jats:p>","DOI":"10.3390\/jcm8060906","type":"journal-article","created":{"date-parts":[[2019,6,25]],"date-time":"2019-06-25T10:52:31Z","timestamp":1561459951000},"page":"906","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Loss of XBP1 Leads to Early-Onset Retinal Neurodegeneration in a Mouse Model of Type I Diabetes"],"prefix":"10.3390","volume":"8","author":[{"given":"Todd","family":"McLaughlin","sequence":"first","affiliation":[{"name":"Departments of Ophthalmology and Ross Eye Institute, University at Buffalo, Buffalo, NY 14203, USA"},{"name":"SUNY Eye Institute, State University of New York, Buffalo, NY 14203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manhal","family":"Siddiqi","sequence":"additional","affiliation":[{"name":"Departments of Ophthalmology and Ross Eye Institute, University at Buffalo, Buffalo, NY 14203, USA"},{"name":"SUNY Eye Institute, State University of New York, Buffalo, NY 14203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua J.","family":"Wang","sequence":"additional","affiliation":[{"name":"Departments of Ophthalmology and Ross Eye Institute, University at Buffalo, Buffalo, NY 14203, USA"},{"name":"SUNY Eye Institute, State University of New York, Buffalo, NY 14203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah X.","family":"Zhang","sequence":"additional","affiliation":[{"name":"Departments of Ophthalmology and Ross Eye Institute, University at Buffalo, Buffalo, NY 14203, USA"},{"name":"SUNY Eye Institute, State University of New York, Buffalo, NY 14203, USA"},{"name":"Department of Biochemistry, State University of New York, Buffalo, NY 14203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,6,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1007\/s11427-015-4856-x","article-title":"Diabetic retinopathy: Recent advances towards understanding neurodegeneration and vision loss","volume":"58","author":"Barber","year":"2015","journal-title":"Sci. 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