TY - JOUR
T1 - Similar effects of selective laser trabeculoplasty and prostaglandin analogs on the permeability of cultured schlemm canal cells
AU - Alvarado, Jorge A.
AU - Iguchi, Rumiko
AU - Martinez, Juan
AU - Trivedi, Sheetal
AU - Shifera, Amde Selassie
N1 - Funding Information:
Publication of this study was supported by a major grant from the Thomas J. Long Foundation , Walnut Creek, California; The Peninsula Community Foundation , Mountain View, California; That Man May See, Inc , San Francisco, California; the Department of Ophthalmology , at University of California at San Francisco, San Franciso, California; Research to Prevent Blindness, Inc , New York, New York; The Joan Leidy Foundation , Hailey, Idaho and contributions from many generous patients of Dr Alvarado. The authors indicate no financial conflict of interest. Involved in Design of study (J.A.A., A.S.S.); Conduct of study (J.A.A., R.I., J.M., S.T., A.S.S.); Statistical analysis (S.T., A.S.S.); Interpretation of data (J.A.A., R.I., J.M., S.T., A.S.S.); and Approval of manuscript (J.A.A., R.I., J.M., S.T., A.S.S.). No human subjects were used in the study. The authors thank Laboratory Associate Linda Franse-Carman and Administrative Assistant Monica Lee for their contribution to this article; and Dr James M. Anderson and Dr Alan Fanning, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, for generously providing us with the pEGFP-C1 ZO-1 plasmid. This article is based on a presentation at the Annual Meeting of the American Ophthalmological Society in May 2009 and subsequently published in the Transactions of the American Ophthalmological Society in December 2009. The manuscript underwent subsequent peer review by the American Journal of Ophthalmology and was modified after the peer review process.
Copyright:
Copyright 2010 Elsevier B.V., All rights reserved.
PY - 2010/8
Y1 - 2010/8
N2 - Purpose: To evaluate whether selective laser trabeculoplasty and prostaglandin analogs regulate the permeability of cultured human Schlemm canal cells by inducing intercellular junction disassembly. Design: Laboratory investigation. Methods: 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. Schlemm canal cells were treated by 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. Junction disassembly was monitored using fluorescence microscopy, and permeability alterations were measured as changes in conductivity using flow meters. Results: The direct laser irradiation of Schlemm canal cells caused a 3-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 2- to 4-fold increase in conductivity. Exposure to prostaglandin analogs also induced junction disassembly and a 4- to 16-fold increase in conductivity, whereas the 3 nonprostaglandin agents tested were ineffective in both regards. Conclusions: Exposure to factors secreted by lasered Schlemm canal cells and lasered trabecular meshwork cells and the application of prostaglandin analogs induced junction disassembly while increasing the permeability of Schlemm canal cells. These findings support our hypothesis that selective laser trabeculoplasty and prostaglandin analogs share a common mechanism that likely mediates their pressure-lowering effects.
AB - Purpose: To evaluate whether selective laser trabeculoplasty and prostaglandin analogs regulate the permeability of cultured human Schlemm canal cells by inducing intercellular junction disassembly. Design: Laboratory investigation. Methods: 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. Schlemm canal cells were treated by 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. Junction disassembly was monitored using fluorescence microscopy, and permeability alterations were measured as changes in conductivity using flow meters. Results: The direct laser irradiation of Schlemm canal cells caused a 3-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 2- to 4-fold increase in conductivity. Exposure to prostaglandin analogs also induced junction disassembly and a 4- to 16-fold increase in conductivity, whereas the 3 nonprostaglandin agents tested were ineffective in both regards. Conclusions: Exposure to factors secreted by lasered Schlemm canal cells and lasered trabecular meshwork cells and the application of prostaglandin analogs induced junction disassembly while increasing the permeability of Schlemm canal cells. These findings support our hypothesis that selective laser trabeculoplasty and prostaglandin analogs share a common mechanism that likely mediates their pressure-lowering effects.
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U2 - 10.1016/j.ajo.2010.03.012
DO - 10.1016/j.ajo.2010.03.012
M3 - Article
C2 - 20570234
AN - SCOPUS:77955495618
SN - 0002-9394
VL - 150
SP - 254
EP - 264
JO - American Journal of Ophthalmology
JF - American Journal of Ophthalmology
IS - 2
ER -