Prostaglandins Increase Trabecular Meshwork Outflow Facility in Cultured Human Anterior Segments

Cindy K. Bahler, Kyle G. Howell, Cheryl R. Hann, Michael P. Fautsch, Douglas H. Johnson

Research output: Contribution to journalArticlepeer-review

77 Scopus citations

Abstract

Purpose: To determine the effect of latanoprost free acid and prostaglandin E1 (PGE1) on outflow facility in cultured human anterior segments. Clinical studies find prostaglandin treatment increases uveoscleral outflow, but do not agree whether trabecular outflow increases. Cultured anterior segments eliminate the uveoscleral pathway and enable a direct assessment of trabecular outflow. Design: Laboratory investigation. Methods: One anterior segment of an eye pair was placed in perfusion organ culture and received a continuous infusion of drug while the fellow anterior segment received vehicle. Histologic changes were assessed. Zymography and Western blots were used to analyze matrix metalloprotease (MMP) activity. Scleral hydraulic conductivities were measured. Results: Latanoprost significantly increased outflow facility (67% ± 11% vs control 6% ± 10%, P < .001). Facility changes occurred within one hour of receiving drug, reaching a new baseline by 24 hours. Facility changes were reversible, requiring about 48 hours to return to pre-drug values. PGE1 caused less facility change (13% ± 17% vs control 1% ± 11%, P = .02). Prostaglandin treated anterior segments had regions of focal detachment and loss of Schlemm canal endothelial cells, with loss of extracellular matrix underlying some areas. MMPs were not consistently increased in Western blots, zymography, or immunohistochemistry. Scleral hydraulic conductivity increased, but not enough to account for total facility increase. Conclusions: Prostaglandins increase outflow facility in perfusion organ culture of human anterior segments. MMP activity was not consistently increased, and scleral hydraulic conductivity was not increased sufficiently to account for total facility increase. The histologic changes suggest a direct trabecular meshwork effect.

Original languageEnglish (US)
Pages (from-to)114-119
Number of pages6
JournalAmerican journal of ophthalmology
Volume145
Issue number1
DOIs
StatePublished - Jan 2008

ASJC Scopus subject areas

  • Ophthalmology

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