Stem cell transplantation rescued a primary open-angle glaucoma mouse model

  1. Siqi Xiong
  2. Ajay Kumar
  3. Shenghe Tian
  4. Eman E Taher
  5. Enzhi Yang
  6. Paul R Kinchington
  7. Xiaobo Xia
  8. Yiqin Du  Is a corresponding author
  1. University of Pittsburgh, United States
  2. Xiangya Hospital, Central South University, China

Abstract

Glaucoma is a leading cause of irreversible blindness. In this study, we investigated if exogenous stem cells are able to rescue a glaucoma mouse model with transgenic myocilin Y437H mutation and explored the possible mechanisms. Human trabecular meshwork stem cells (TMSCs) were intracamerally transplanted which reduced mouse intraocular pressure, increased outflow facility, protected the retinal ganglion cells and preserved their function. TMSC transplantation also significantly increased the TM cellularity, promoted myocilin secretion from TM cells into the aqueous humor to reduce endoplasmic reticulum stress, repaired the TM tissue with extracellular matrix modulation and ultrastructural restoration. Co-culturing TMSCs with myocilin mutant TM cells in vitro promoted TMSCs differentiating into phagocytic functional TM cells. RNA sequencing revealed that TMSCs had upregulated genes related to TM regeneration and neuroprotection. Our results uncovered therapeutic potential of TMSCs for curing glaucoma and elucidated possible mechanisms by which TMSCs achieve the treatment effect.

Data availability

All data generated or analyzed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 1 through 9.

Article and author information

Author details

  1. Siqi Xiong

    Ophthalmology, University of Pittsburgh, Pittsburgh, United States
    Competing interests
    No competing interests declared.
  2. Ajay Kumar

    Ophthalmology, University of Pittsburgh, Pittsburgh, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3412-1823
  3. Shenghe Tian

    Ophthalmology, University of Pittsburgh, Pittsburgh, United States
    Competing interests
    No competing interests declared.
  4. Eman E Taher

    Ophthalmology, University of Pittsburgh, Pittsburgh, United States
    Competing interests
    No competing interests declared.
  5. Enzhi Yang

    Ophthalmology, University of Pittsburgh, Pittsburgh, United States
    Competing interests
    No competing interests declared.
  6. Paul R Kinchington

    Ophthalmology, University of Pittsburgh, Pittsburgh, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1901-9970
  7. Xiaobo Xia

    Ophthalmology, Xiangya Hospital, Central South University, Changsha, China
    Competing interests
    No competing interests declared.
  8. Yiqin Du

    Ophthalmology & Developmental Biology, University of Pittsburgh, Pittsburgh, United States
    For correspondence
    duy@upmc.edu
    Competing interests
    Yiqin Du, The University of Pittsburgh has a competing interest with a patent named trabecular meshwork stem cells" with Yiqin Du as one of the inventors.".
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4330-0957

Funding

National Eye Institute (EY025643)

  • Yiqin Du

National Eye Institute (P30-EY008098)

  • Yiqin Du

Research to Prevent Blindness

  • Yiqin Du

Eye and Ear Foundation of Pittsburgh

  • Yiqin Du

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All the experiments conducted on the animals were approved by the University of Pittsburgh Institutional Animal Care (protocol 18022317) and Use Committee and complied with the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research. Human cell culture was approved by the Committee for Oversignt of Research and Clinical Training Involving Decedents (CORID No. 161).

Reviewing Editor

  1. Martin Pera, The Jackson Laboratory, United States

Publication history

  1. Received: October 2, 2020
  2. Accepted: January 22, 2021
  3. Accepted Manuscript published: January 28, 2021 (version 1)
  4. Version of Record published: February 4, 2021 (version 2)

Copyright

© 2021, Xiong et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Siqi Xiong
  2. Ajay Kumar
  3. Shenghe Tian
  4. Eman E Taher
  5. Enzhi Yang
  6. Paul R Kinchington
  7. Xiaobo Xia
  8. Yiqin Du
(2021)
Stem cell transplantation rescued a primary open-angle glaucoma mouse model
eLife 10:e63677.
https://doi.org/10.7554/eLife.63677

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