BPB Reports

Paper Details

BPB Reports
Vol. 3 No. 3 p.92-96 2020
Regular Article
Tauroursodeoxycholic Acid Promotes Neuronal Survival and Proliferation of Tissue Resident Stem and Progenitor Cells in Retina of Adult Zebrafish
  • Mikiko Nagashima (Department of Ophthalmology and Visual Sciences, University of Michigan / mikiko@umich.edu)
  • Masamitsu Shimazawa (Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University / Department of Biomedical Research, Gifu Pharmaceutical University / shimazawa@gifu-pu.ac.jp)
Yuichi Saito 1) 2) , Hiroyuki Okuyoshi 1) , Shinsuke Nakamura 1) , Wataru Otsu 3) , Akihiro Yamaguchi 1) , Peter F. Hitchcock 2) , Mikiko Nagashima 2) , Masamitsu Shimazawa 1) 3) , Hideaki Hara 1) 3)
1) Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University , 2) Department of Ophthalmology and Visual Sciences, University of Michigan , 3) Department of Biomedical Research, Gifu Pharmaceutical University
Received: March 26, 2020;   Accepted: May 12, 2020;   Released: May 26, 2020
Keywords: bile acid, stem cells, Müller glia, cyclin dependent kinase inhibitor
Abstracts

Regenerative medicine aims to replenish damaged tissue. Boosting the capacity of intrinsic stem cells to proliferate is one key for successful regeneration. Adult zebrafish possess tissue resident stem and progenitor cells, which contribute to homeostatic growth and tissue regeneration. In the intact retina, Müller glia sporadically divide to generate fate restricted, proliferative precursors. Cell death reprograms Müller glia into stem cells that divide and produce multi-potent retinal progenitors. Using zebrafish, we evaluated the effect of taurine-conjugated bile acid, Tauroursodeoxycholic acid (TUDCA) on retinal regeneration. In the intact retina, treatment with TUDCA significantly promotes proliferation of the fate restricted precursors, but has no effect on Müller glia. Following constant light exposure, TUDCA attenuates photoreceptor death, indicating that TUDCA is neuroprotective. Following a stab wound, which initiates death of retinal neurons and reprogramming of Müller glia, treatment with TUDCA significantly increases the number of proliferating cells. In the intact retina, TUDCA-induced proliferation was accompanied by decreased expression of cell cycle inhibitors. These results suggest that TUDCA promotes proliferation of actively-cycling stem and progenitors, identifying TUDCA as a potential reagent to promote regeneration of retinal neurons.