Modulation of the Rate of Retinal Degeneration in T17M RHO Mice by Reprogramming the Unfolded Protein Response.

  • Shreyasi Choudhury
  • Sonali Nashine
  • Yogesh Bhootada
  • Mansi Motiwale Kunte
  • Oleg Gorbatyuk
  • Alfred S. Lewin
  • Marina Gorbatyuk
Conference paper

DOI: 10.1007/978-1-4614-3209-8_58

Volume 801 of the book series Advances in Experimental Medicine and Biology
Cite this paper as:
Choudhury S. et al. (2014) Modulation of the Rate of Retinal Degeneration in T17M RHO Mice by Reprogramming the Unfolded Protein Response.. In: Ash J., Grimm C., Hollyfield J., Anderson R., LaVail M., Bowes Rickman C. (eds) Retinal Degenerative Diseases. Advances in Experimental Medicine and Biology, vol 801. Springer, New York, NY

Abstract

The goal of this study is to validate whether reprogramming of the UPR via modulation of pro-apoptotic caspase-7 and CHOP proteins could be an effective approach to slow down the rate of retinal degeneration in ADRP mice. In order to pursue our goal we created the T17M RHO CASP7 and T17M RHO CHOP mice to study the impact of the CASP7 or CHOP ablations in T17M RHO retina by ERG, SD-OCT, histology and western blot analysis. The scotopic ERG demonstrated that the ablation of the CASP7 in T17M RHO retina leads to significant preservation of the function of photoreceptors compared to control. Surprisingly, the ablation of pro-apoptotic CHOP protein in T17M RHO mice led to a more severe form of retinal degeneration. Results of the SD-OCT and histology were in agreement with the ERG data. The further analysis demonstrated that the preservation of the structure and function or the acceleration of the onset of the T17M RHO photoreceptor degeneration occurred via reprogramming of the UPR. In addition, the CASP7 ablation leads to the inhibition of cJUN mediated apoptosis, while the ablation of CHOP induces an increase in the HDAC. Thus, manipulation with the UPR requires careful examination in order to achieve a therapeutic effect.

Keywords

ADRP UPR Caspase-7 CHOP Apoptosis 

Copyright information

© Springer Science+Business Media, LLC 2014

Authors and Affiliations

  • Shreyasi Choudhury
    • 1
  • Sonali Nashine
    • 1
  • Yogesh Bhootada
    • 2
  • Mansi Motiwale Kunte
    • 1
  • Oleg Gorbatyuk
    • 3
  • Alfred S. Lewin
    • 3
  • Marina Gorbatyuk
    • 2
    • 4
  1. 1.Department of Cell Biology and AnatomyUniversity of North Texas Health Science CenterFort WorthUSA
  2. 2.Department of Molecular Genetics and MicrobiologyUniversity of FloridaGainesvilleUSA
  3. 3.Department of Vision SciencesUniversity of Alabama at BirminghamBirminghamUSA
  4. 4.BirminghamUSA