PT  - JOURNAL ARTICLE
AU  - Siqi Xiong
AU  - Ajay Kumar
AU  - Shenghe Tian
AU  - Eman E. Taher
AU  - Enzhi Yang
AU  - Paul R. Kinchington
AU  - Xiaobo Xia
AU  - Yiqin Du
TI  - Stem Cell Transplantation Rescued A Primary Open-Angle Glaucoma Mouse Model
AID  - 10.1101/2020.02.04.934448
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.02.04.934448
4099  - http://biorxiv.org/content/early/2020/11/06/2020.02.04.934448.short
4100  - http://biorxiv.org/content/early/2020/11/06/2020.02.04.934448.full
AB  - 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.Competing Interest StatementThe University of Pittsburgh has a competing interest with a patent named "trabecular meshwork stem cells" with Yiqin Du as one of the inventors.