Loss of the cone-enriched does not affect secondary cone death in retinitis pigmentosa.

PURPOSE

The apoptotic mechanisms responsible for secondary cone death in retinitis pigmentosa (RP) remain largely unknown. The cone-enriched apoptotic protease () is thought to be triggered by endoplasmic reticulum (ER) stress and plays a pivotal role in mice deficient in the cone cyclic nucleotide-gated channels, a deficiency that causes achromatopsia in humans and in mice with autosomal dominant rhodopsin mutations, in particular the T17M mutation. Thus, we tested in two mouse models of RP whether the cone-enriched plays a role during secondary cone death.

METHODS

knockout mice were crossed to two different RP mouse models with significantly different rod and cone death kinetics: the mouse model, which carries a mutation in the gene, and the rhodopsin knockout mouse model ( or ). In both models, cone survival was assessed on retinal flat mounts by quantifying the percentage of cone arrestin staining over the retinal surface area. The analyses were performed at two different time points for each model.

RESULTS

Loss of did not alter cone survival in either of the two mouse models tested regardless of the time point analyzed. Rod survival was also not affected in either model nor did loss of affect rod or cone function in a wild-type background as assessed with electroretinogram analyses.

CONCLUSIONS

Secondary cone death in retinitis pigmentosa is unlikely to be triggered by ER stress and is likely independent of activity.