Abstract
Purpose: :
Cellular trabecular meshwork (TM) loss in primary open angle glaucoma likely contributes to loss of IOP regulation. Studies were conducted to determine if replacement cells can be transplanted to partially denuded anterior segments to restore IOP homeostatic capability. Replacing lost or dead TM cells with functional transplanted stem cells could be an alternative treatment for glaucoma.
Methods: :
Saponin treatment was used to partially denude human anterior segments. Flow properties of anterior segments with denuded human trabecular meshwork (HTM) were evaluated in perfusion culture in a model system for flow, and examined by immunohistochemistry and confocal microscopy. Repopulation of denuded explants with human mesenchymal stem cells (hMSC) and HTM cells was evaluated. HMSC were co-cultured with HTM cells and allowed to ingest zymosan particles, an assay for TM cell phagocytic function.
Results: :
Anterior segments treated with saponin flowed normally in the model flow system, but lost the capacity for IOP homeostatic responses to pressure elevation. Both HTM cells and hMSC transplanted to denuded anterior segments were capable of restoring IOP homeostatic pressure responses. Labeled hMSC, after co-culture with HTM, ingested zymosan particles, while hMSC cultured alone did not.
Conclusions: :
TM denuded by saponin in anterior segments loses IOP homeostatic capability. Addition of hMSC and HTM cells to such segments restored this IOP response. Co-culturing hMSC with HTM allows hMSC to develop HTM phagocytic abilities. Patient-specific hMSC transplanted to the TM may have the potential to functionally replace TM cells normally lost in glaucoma.
Keywords: trabecular meshwork • transplantation • outflow: trabecular meshwork