Rescue of cochlear vascular pathology prevents sensory hair cell loss in Norrie disease.

ABSTRACT: Variants in the gene NDP cause Norrie disease, a severe dual-sensory disorder characterized by congenital blindness due to disrupted retinal vascular development and progressive hearing loss accompanied by sensory hair cell death. NDP encodes the secreted signaling molecule norrin. The role of norrin in the cochlea is incompletely understood. We investigated whether the Norrie disease cochlear pathology can be ameliorated in an Ndp-knockout (Ndp-KO) mouse model by conditional activation of stabilized β-catenin in vascular endothelial cells. We hypothesized that in the cochlea microvasculature, β-catenin is the primary downstream intracellular effector of norrin binding to endothelial cell surface receptors and that restoration of this signaling pathway is suffic

SUBMITTER: Patel A 

PROVIDER: S-EPMC11626139 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature