Abstract
Purpose :
To explore the hypothesis that chemokines are associated with human trabecular meshwork stem cell (TMSC) homing to the TM tissue for TM regeneration and intraocular pressure regulation.
Methods :
Human TMSCs were cultured and passaged as previously described. TMSCs were plated directly onto cell culture dishes or on to dishes pre-seeded with TM cells as feeders. Attached TMSCs at 30 min and 60 min were counted and compared. Primary TM cells and fibroblasts served as controls. TMSCs or TMSCs treated with CXCR4 inhibitor were seeded on cell culture inserts with different attractants on the bottom. Percentage of cell number migrated down through the insert membrane was compared in different conditions. Chemokine expression of TMSCs and TM cells were detected by qPCR. Mouse chemokine expression on mouse TM tissue with and without laser photocoagulation was determined by qPCR. TMSCs were intracamerally injected into partially laser-treated mice and TMSC distribution was detected by wholemount staining.
Results :
Human TMSCs have higher affinity to the TM cells than TM cells and fibroblasts to the TM cells. TM cells with increased expression of SDF1 are the highest attractant to TMSCs. TMSCs with reduced expression of CXCR4 have less affinity to TM cells. After laser treatment, the mouse TM cells had increased expression of CXCR4 and SDF1. Injected TMSCs specifically homed to laser damaged mouse TM region and reduced intraocular pressure (IOP).
Conclusions :
TMSCs have higher expression of CXCR4 while TM cells have higher expression of SDF1. Chemokines CXCR4-SDF1 play important roles in TM stem cell homing for TM regeneration and IOP regulation.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.