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Related Experiment Video

Updated: Nov 19, 2025

Transpupillary-Guided Trans-Scleral Transplantation of Subretinal Grafts in a Retinal Degeneration Mouse Model
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Stem cell transplantation rescued a primary open-angle glaucoma mouse model.

Siqi Xiong1,2,3, Ajay Kumar1, Shenghe Tian1

  • 1Department of Ophthalmology, University of Pittsburgh, Pittsburgh, United States.

Elife
|January 28, 2021
PubMed
Summary

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Transplanted human trabecular meshwork stem cells (TMSCs) effectively treated a glaucoma mouse model. These stem cells reduced intraocular pressure and protected vision by regenerating eye tissues and reducing cellular stress.

Area of Science:

  • Ophthalmology
  • Regenerative Medicine
  • Cell Biology

Background:

  • Glaucoma is a primary cause of irreversible blindness worldwide.
  • Genetic mutations, such as in myocilin, can lead to glaucoma by affecting trabecular meshwork (TM) function.
  • Current treatments aim to lower intraocular pressure but do not restore damaged tissues.

Purpose of the Study:

  • To investigate the therapeutic potential of human trabecular meshwork stem cells (TMSCs) in a mouse model of glaucoma.
  • To elucidate the mechanisms by which TMSCs exert their therapeutic effects in glaucoma.

Main Methods:

  • Intracameral transplantation of TMSCs into a glaucoma mouse model with a transgenic myocilin Y437H mutation.
  • Assessment of intraocular pressure, outflow facility, and retinal ganglion cell function.
Keywords:
RNAseqglaucomahumanmousemouse modelregenerative medicinestem cellstrabecular meshworktransplantation

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  • Analysis of TM cellularity, extracellular matrix, endoplasmic reticulum stress markers, and gene expression via RNA sequencing.
  • In vitro co-culturing of TMSCs with myocilin mutant TM cells.

    • Main Results:

    • TMSC transplantation significantly reduced intraocular pressure and improved outflow facility.
    • Transplanted TMSCs protected retinal ganglion cells and preserved their function.
    • TMSC treatment increased TM cellularity, promoted myocilin secretion, reduced endoplasmic reticulum stress, and restored TM tissue structure.
    • In vitro studies showed TMSCs differentiating into functional TM cells, and RNA sequencing revealed upregulated genes related to TM regeneration and neuroprotection.

    Conclusions:

    • Transplanted TMSCs demonstrate significant therapeutic potential for treating glaucoma.
    • TMSCs exert their effects through multiple mechanisms including tissue regeneration, stress reduction, and neuroprotection.
    • This study provides a foundation for developing novel stem cell-based therapies for glaucoma.