Abstract

Retinal degenerative diseases, due to the lack of regeneration systems and self-renewable cells, often lead to visual impairment. Pax6 is a pleiotropic transcription factor and its expression level determines self-renewal status or differentiation of retinal cells. Here, we investigated the fate of simultaneous induction of retinal ganglion cell death and Pax6 overexpression in retro-differentiation of retinal cells and their commitment to re-enter into the cell cycle. Induction of acute retinal ganglion cell death and generation of mouse experimental model was performed by N-methyl D-aspartic acid (NMDA) injection. Recombinant AAV2 virus harboring PAX6 cDNA and reporter gene was injected into untreated and model mouse eyes. Histological analyses, including IHC and retinal flatmounts immunostaining were performed. The number of Ki67+ cells was clearly increased in model mice, presumably due to NMDA treatment and regardless of Pax6 over-expression. Unlike previous studies, Ki67+ cells were found in GCL layer and interestingly ONL cells expressed Sox2 stemness marker after NMDA cytotoxicity. The potential of retinal cells for robust Ki67 expression, after injury, and expression of Sox2, confirmed their intrinsic plasticity and made a vivid prospect for retinal regenerative medicine.

Details

Title
In Vivo Evaluation of PAX6 Overexpression and NMDA Cytotoxicity to Stimulate Proliferation in the Mouse Retina
Author
Pirmardan, Ehsan Ranaei 1 ; Zahra-Soheila Soheili 2 ; Samiei, Shahram 3 ; Ahmadieh, Hamid 4 ; Mowla, Seyed Javad 1 ; Naseri, Marzieh 5 ; Daftarian, Narsis 4 

 Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran 
 Department of Molecular Medicine, Institute of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran 
 Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran 
 Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran 
 Department of Molecular Medicine, Faculty of Advanced Technology, Iran University of Medical Sciences, Tehran, Iran 
Pages
1-10
Publication year
2018
Publication date
Dec 2018
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2151750109
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.