From the bedside to the bench and back again: Predicting and improving the outcomes of SLT glaucoma therapy

Jorge A. Alvarado, Rumiko Iguchi, Richard Juster, Julie A. Chen, Amde Selassie Shifera

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Purpose: To determine whether selective laser trabeculoplasty (SLT) and prostaglandin analogues (PGAs) have a common mechanism of action that involves increasing conductivity across Schlemm's canal endothelial cells (SCEs) and inducing a similar decrease in intraocular pressure (IOP) in a given patient. Methods: The intercellular junctions in SCEs were made visible by transfection of a plasmid containing a GFP-tagged gene for ZO-1 protein. Transfected SCEs were treated with media conditioned by lasered trabecular meshwork endothelial cells (TMEs), or with latanoprost, bimatoprost, or travoprost. Non-transfected SCEs were exposed to brimonidine, timolol, or brinzolamide. Confocal microscopy and conductivity measurements documented the in vitro treatment effects. Clinically, the IOP in the first SLT-treated eye of 24 patients was measured (1) while on PGA therapy, (2) at "baseline" several weeks after discontinuing PGA therapy, and (3) ∼90 days after SLT treatment. Results: Both the in vitro addition of any of the 3 PGAs and of media conditioned by lasered TMEs induced similar SCE effects involving junction disassembly, paracellular pathway widening, and increased conductivity. Clinically, PGAs decreased IOP by a mean of 5.58 mmHg and SLT decreased IOP by 6.60 mmHg from a baseline of 21.52 mmHg. Conclusions: Exposure to media conditioned by lasered TMEs, or the addition of PGAs, induces the disassembly of intercellular junctions opening up the SCE barrier. Clinically, a positive PGA response predicts both a successful SLT outcome and the magnitude of the decrease in IOP after SLT. We hypothesize that SLT and PGA therapies may share a common mechanism of action.

Original languageEnglish (US)
Pages (from-to)167-181
Number of pages15
JournalTransactions of the American Ophthalmological Society
Volume107
StatePublished - Dec 1 2009
Externally publishedYes

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ASJC Scopus subject areas

  • Ophthalmology

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