Abstract
Purpose:
Usher syndrome combines congenital hearing loss and retinitis pigmentosa (RP). Mutations in the whirlin gene (DFNB31/WHRN) cause a subtype of Usher syndrome (USH2D). Whirler mice have inner ear defects but do not develop retinal degeneration. Here we investigate abnormalities in whirler mouse photoreceptors.
Methods:
Immunohistochemistry, serial tangential section immunoblotting and hydroethidine-based detection of intracellular superoxide production were used. Photoreceptor cell densities under various conditions of light/dark exposures were evaluated.
Results:
In whirler mouse photoreceptors, the light-activated rod transducin translocation is delayed and its activation threshold is shifted to a higher level. Rhodopsin is observed in the connecting cilia of rods. Continuous moderate light exposure induced significant rod photoreceptor degeneration and superoxide accumulation. Whirler mice reared under a 1500 lux light/dark cycle also resulted in significant photoreceptor degeneration. Previously, we reported that shaker1 mice, a USH1B model, also showed moderate light-induced photoreceptor degeneration with delayed transducin translocation.
Conclusions:
The results from shaker1 and whirler mice suggest that defective transducin translocation is linked to light-induced degeneration, and these two symptoms may reflect defects in rod photoreceptors. These results also indicate that both Usher syndrome mouse models may share a closely related pathobiological mechanism for retinal degeneration.
Keywords: 695 retinal degenerations: cell biology •
648 photoreceptors •
539 genetics