Synaptic alterations are preceding the axonal loss in optic atrophy of Wolfram syndrome mouse model

BackgroundWolfram 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 WFS1 gene, which encodes a transmembrane endoplasmic reticulum–resident protein involved in the unfolded protein response and cellular calcium homeostasis. Although multipl