Congratulations to the Dinculescu and Link labs on the publication of “The USH3A causative gene clarin1 functions in Müller glia to maintain retinal photoreceptors”, which has been accepted for publication in PLOS Genetics [2025 Mar 11;21(3): e1011205.Online ahead of print]
Usher syndrome (USH) is an autosomal recessive disorder characterized by the loss of both hearing and vision. Mutations in USH-associated genes profoundly impact patients, affecting auditory, visual, and vestibular function. In USH3A, the affected gene, clarin1 (clrn1), is predominantly expressed in Müller glia in the retina. The role of Müller glia in maintaining the health of light-sensitive photoreceptor neurons is understudied, in part as Clrn1 mutant mice – the traditional experimental model used to study retinal diseases – do not phenocopy the photoreceptor loss of USH3 patients. In the present study, we developed a zebrafish model of USH3A that displays many features of the human disease. Our research shows that the loss of Clrn1 affects actin-based structures of the outer retina, including those of Müller glia and photoreceptors. Importantly, we demonstrate that the expression of Clrn1 in Müller glia, but not photoreceptors, alleviated light-induced damage in clrn1 mutant zebrafish. We also highlight that the dosage of Clrn1 in Müller glia is critical for maintaining proper photoreceptor function. These findings demonstrate the key contribution of Müller glia to USH pathology and can guide strategies for gene-replacement therapies.