Stem cell transplantation rescued a primary open-angle glaucoma mouse model
Siqi Xiong,
Ajay Kumar,
Shenghe Tian,
Eman E Taher,
Enzhi Yang,
Paul R Kinchington,
Xiaobo Xia,
Yiqin Du
Affiliations
Siqi Xiong
Department of Ophthalmology, University of Pittsburgh, Pittsburgh, United States; Eye Center of Xiangya Hospital, Central South University, Changsha, China; Hunan Key Laboratory of Ophthalmology, Changsha, China
Department of Ophthalmology, University of Pittsburgh, Pittsburgh, United States; Department of Developmental Biology, University of Pittsburgh, Pittsburgh, United States; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, United States
Glaucoma is a leading cause of irreversible blindness. In this study, we investigated if transplanted 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.
