Department of Ophthalmology; Gene Therapy Center; UMass Metabolic Network
Cellular and Molecular Physiology | Enzymes and Coenzymes | Eye Diseases | Molecular Biology | Ophthalmology
Purpose: The apoptotic mechanisms responsible for secondary cone death in retinitis pigmentosa (RP) remain largely unknown. The cone-enriched apoptotic protease caspase-7 (Casp7) 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 Casp7 plays a role during secondary cone death.
Methods: Casp7 knockout mice were crossed to two different RP mouse models with significantly different rod and cone death kinetics: the rd1 mouse model, which carries a mutation in the Pde6b gene, and the rhodopsin knockout mouse model (Rho-KO or Rho(-/-) ). 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 Casp7 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 Casp7 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 Casp7 activity.
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Copyright © 2017 Molecular Vision. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited, used for non-commercial purposes, and is not altered or transformed.
Mol Vis. 2017 Dec 15;23:944-951. eCollection 2017.
Venkatesh, Aditya; Cheng, Shun-Yun; and Punzo, Claudio, "Loss of the cone-enriched caspase-7 does not affect secondary cone death in retinitis pigmentosa" (2017). University of Massachusetts Medical School Faculty Publications. 1474.