Abstract
Glaucoma is the leading cause of irreversible vision loss, and reducing elevated intraocular pressure is currently the only effective clinical treatment. The trabecular meshwork is the main resistance site for aqueous outflow that maintains intraocular pressure. In this study, we transplanted human trabecular meshwork stem cells (TMSCs) intracamerally into mice that received laser photocoagulation over a 180° arc of the trabecular meshwork. TMSCs preferentially homed and integrated to the laser-damaged trabecular meshwork region and expressed differentiated cell markers at 2 and 4 weeks. Laser-induced inflammatory and fibrotic responses were prevented by TMSC transplantation with simultaneous ultrastructure and function restoration. Cell affinity and migration assays and elevated expression of CXCR4 and SDF1 in laser-treated mouse trabecular meshwork suggest that the CXCR4/SDF1 chemokine axis plays an important role in TMSC homing. Our results suggest that TMSCs may be a viable candidate for trabecular meshwork refunctionalization as a novel treatment for glaucoma.
Highlights
Studies on human eyes that received laser trabeculoplasty[15] showed that there was a population of trabecular meshwork cells that underwent increased cell division and migration to repopulate the damaged trabecular meshwork
We developed a new mouse model wherein a half circumference of trabecular meshwork tissue was injured by laser photocoagulation, allowing us to test the ability of trabecular meshwork stem cells (TMSCs) to home to damaged trabecular meshwork tissue and restore the structure and function of the trabecular meshwork
Our data show that TMSCs preferentially home to the laser-damaged trabecular meshwork region and integrate into the trabecular meshwork tissue after intracameral injection
Summary
Studies on human eyes that received laser trabeculoplasty[15] showed that there was a population of trabecular meshwork cells that underwent increased cell division and migration to repopulate the damaged trabecular meshwork. This has motivated study into the use of stem cells to repopulate and refunctionalize the trabecular meshwork and reduce IOP in glaucoma patients. Stem cells are characterized by asymmetric cell division, selfrenewal, and the ability to generate differentiated daughter cells They are capable of multilineage differentiation and functional reconstruction of damaged tissues in vivo[16]. Our study shows that stem cell-based therapy is feasible as a new approach to restore glaucomatous trabecular meshwork function
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