{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:13:55Z","timestamp":1785428035999,"version":"3.56.0"},"posted":{"date-parts":[[2026,3,25]]},"group-title":"Neuroscience","reference-count":43,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T00:00:00Z","timestamp":1774396800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"award":["DK132090"],"award-info":[{"award-number":["DK132090"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["DK020579"],"award-info":[{"award-number":["DK020579"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,3,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Wolfram syndrome is a rare autosomal recessive disorder characterized by antibody-negative early-onset diabetes mellitus, optic atrophy, sensorineural hearing loss, arginine-vasopressin deficiency, and progressive neurodegeneration of the brainstem and cerebellum. It is caused primarily by pathogenic variants in the\n                  <jats:italic>WFS1<\/jats:italic>\n                  gene, which encodes a transmembrane endoplasmic reticulum-resident protein involved in the unfolded protein response and cellular calcium homeostasis. Although multiple rodent models of Wolfram syndrome have been developed and shown to exhibit visual defects, some studies have reported significant vision loss prior to any detectable axonal degeneration or myelin abnormalities, and the mechanisms underlying these early visual deficits remain poorly understood. Recent\n                  <jats:italic>in vitro<\/jats:italic>\n                  studies have demonstrated altered synaptic contacts and aberrant neurite morphology in\n                  <jats:italic>WFS1<\/jats:italic>\n                  -deficient cerebral organoids and human iPSC-derived neurons, respectively. These findings prompted us to investigate, for the first time in vivo, whether synaptic and dendritic abnormalities occur in the retina of\n                  <jats:italic>Wfs1<\/jats:italic>\n                  knockout mice. Using confocal microscopy, we examined retinal and optic nerve histology in\n                  <jats:italic>Wfs1<\/jats:italic>\n                  knockout mice at 4 and 7 months of age. Our analysis reveals progressive synaptic alterations in the inner plexiform layer, driven by early presynaptic compartment failure. These changes represent the earliest detectable phenotype associated with vision loss in this model and precede overt axonal degeneration.\n                <\/jats:p>","DOI":"10.64898\/2026.03.22.713521","type":"posted-content","created":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T22:30:11Z","timestamp":1774477811000},"source":"Crossref","is-referenced-by-count":1,"title":["Synaptic Alterations Are Preceding the Axonal Loss in Optic Atrophy of Wolfram Syndrome Mouse Model"],"prefix":"10.64898","author":[{"given":"Venu","family":"Gurram","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Endocrinology, Metabolism, and Lipid Research, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"An","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Endocrinology, Metabolism, and Lipid Research, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shrinivas","family":"Bimal","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Endocrinology, Metabolism, and Lipid Research, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9944-6293","authenticated-orcid":false,"given":"Fumihiko","family":"Urano","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Endocrinology, Metabolism, and Lipid Research, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA"},{"name":"Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026032808350964000_2026.03.22.713521v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(95)92473-6"},{"key":"2026032808350964000_2026.03.22.713521v1.2","doi-asserted-by":"crossref","unstructured":"V. Caruso , A. Raia , and L. Rigoli , Wolfram Syndrome 1: A Neuropsychiatric Perspective on a Rare Disease. Genes (Basel) 15 (2024).","DOI":"10.20944\/preprints202407.0604.v1"},{"key":"2026032808350964000_2026.03.22.713521v1.3","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.42.6.1220"},{"key":"2026032808350964000_2026.03.22.713521v1.4","doi-asserted-by":"publisher","DOI":"10.1007\/s11892-015-0702-6"},{"key":"2026032808350964000_2026.03.22.713521v1.5","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2023.1198171"},{"key":"2026032808350964000_2026.03.22.713521v1.6","doi-asserted-by":"publisher","DOI":"10.1038\/2441"},{"key":"2026032808350964000_2026.03.22.713521v1.7","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddg214"},{"key":"2026032808350964000_2026.03.22.713521v1.8","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddm296"},{"key":"2026032808350964000_2026.03.22.713521v1.9","doi-asserted-by":"crossref","unstructured":"C. Angebault , J. Fauconnier , S. Patergnani , J. 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