OCT 26, 2010
This study's authors used a unique in vitro system to demonstrate the effects of various stimuli on the hydraulic conductivity of cultured human Schlemm canal cells. Their findings support their hypothesis that selective laser trabeculoplasty and prostaglandin analogs share a common mechanism that likely mediates their pressure-lowering effects. This may explain the observation that laser irradiation is less effective in patients who have used prostaglandin analogs.
The authors treated Schlemm canal cells with direct laser irradiation; by exposure to media conditioned by either lasered Schlemm canal cells or trabecular meshwork cells; by exposure to the prostaglandin analogs latanoprost, bimatoprost and travoprost; or by the addition of the nonprostaglandin agents brimonidine, timolol and dorzolamide. They monitored junction disassembly using fluorescence microscopy, and changes in permeability were measured as changes in conductivity using flow meters. Intercellular junctions were made visible in living cells by making them fluoresce after transfection with a plasmid expressing the zonula occludens 1 protein tagged with green fluorescent protein.
Direct laser irradiation of Schlemm canal cells caused a three-fold increase in conductivity. Exposure of the cells to media conditioned by lasered Schlemm canal cells or trabecular meshwork cells induced junction disassembly and a two- to four-fold increase in conductivity. Exposure to prostaglandin analogs also induced junction disassembly and a four- to 16-fold increase in conductivity, whereas the three nonprostaglandin agents tested were ineffective in both regards.
The study's findings are novel and exciting. This distinctive set of experiments offers insight into the potential alternative mechanisms of prostaglandins and selective laser trabeculoplasty, which appear to share a common pathway related to increased hydraulic conductivity. Furthermore, laser treatment appears to affect Schlemm canal cells when applied directly and indirectly through mediators secreted from lasered trabecular meshwork cells.
Whether these effects can be demonstrated in vivo will hopefully be determined in future studies. It would also be interesting to determine in vivo if pretreatment with selective laser trabeculoplasty affects the response to prostaglandin treatment or vice versa or whether there is a dose response plateau when Schlemm canal cells are exposed to laser and prostaglandin treatment simultaneously. The latter would confirm the clinical observation of a poor response to selective laser trabeculoplasty in eyes previously treated with prostaglandins. Future studies should also examine if selective laser trabeculoplasty's effects are unique or if treatment of cells in vitro with conventional argon laser radiation produces similar effects. Such research may help avoid the use of redundant treatment.