COMMENTARY

Mechanisms of Intraocular Pressure-Lowering Agents

Rod Foroozan, MD

Disclosures

April 18, 2008

Introduction

Prostaglandins have been shown to play an important role in the balance of aqueous humor outflow. Latanoprost is an important topical agent that lowers intraocular pressure (IOP), largely by increasing uveoscleral outflow. These changes are thought to occur through changes in matrix metalloproteases (MMPs),[1] but there has been conflicting evidence regarding whether trabecular outflow is altered by latanoprost and other prostaglandins. The authors of this study assessed the effect of prostaglandin E1 (PGE) and latanoprost on trabecular outflow facility.

Prostaglandins Increase Trabecular Meshwork Outflow Facility in Cultured Human Anterior Segments

Bahler CK, Howell KG, Hann CR, Fautsch MP, Johnson DH
Am J Ophthalmol. 2008;145:114-119

Summary

This laboratory study used perfusion of cultured human anterior segments. All eyes were enucleated within 4 hours of the time of death, and no eyes had a history of glaucoma. One anterior segment was perfused with a continuous amount of drug and the fellow anterior chamber was monitored without drug. Histologic changes and assessment of MMP activity was then performed. This model was partly chosen because it eliminates the role of the uveoscleral pathway because of absence of the choroid and a functioning ciliary body.

Latanoprost increased outflow facility (an increase of 67%), with changes occurring within 1 hour of receiving drug, whereas PGE caused less of a change in outflow (an increase of 13%) facility. These changes were reversible after the drugs were removed. Histopathologic specimens showed focal detachment and loss of endothelial cells within the canal of Schlemm. There was no consistent pattern of MMP activity. Although scleral hydraulic conductivity increased, the change was not enough to account for the entire change in outflow facility.

Comment

Based on 2 main lines of evidence, the authors suggested that a pressure-sensitive mechanism for the outflow of aqueous humor is important. First, they pointed to an absence of changes in MMPs in the trabecular meshwork. If changes in the trabecular meshwork were solely responsible for the decreases in IOP seen with prostaglandins, then changes in MMP activity would be expected. The second piece of evidence was based on fluid flow through the sclera. Because scleral outflow was measured to be lower than the outflow facility, trabecular outflow appears to be increased by prostaglandins. The authors suggest that because of this mechanism, future drug and gene therapy targets in glaucoma might be influenced.

Abstract

Comments

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