Lysosomal membrane permeabilization and autophagy blockade contribute to photoreceptor cell death in a mouse model of retinitis pigmentosa.

ABSTRACT: Retinitis pigmentosa is a group of hereditary retinal dystrophies that normally result in photoreceptor cell death and vision loss both in animal models and in affected patients. The rd10 mouse, which carries a missense mutation in the Pde6b gene, has been used to characterize the underlying pathophysiology and develop therapies for this devastating and incurable disease. Here we show that increased photoreceptor cell death in the rd10 mouse retina is associated with calcium overload and calpain activation, both of which are observed before the appearance of signs of cell degeneration. These changes are accompanied by an increase in the activity of the lysosomal protease cathepsin B in the cytoplasm of photoreceptor cells, and a reduced colocalization of cathepsin B with lysosomal markers,

SUBMITTER: Rodriguez-Muela N 

PROVIDER: S-EPMC4326579 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature