From the bedside to the bench and back again: predicting and improving the outcomes of SLT glaucoma therapy.
OBJECTIVE
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) approximately 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.
Alvarado
Jorge A
JA
Beckman Vision Center, Department of Ophthalmology, University of California San Francisco.
Iguchi
Rumiko
R
Juster
Richard
R
Chen
Julie A
JA
Shifera
Amde Selassie
AS
D000818:Animals; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004285:Dogs; D042783:Endothelial Cells / Q000187:drug effects / Q000528:radiation effects; D005901:Glaucoma / Q000188:drug therapy* / Q000503:physiopathology / Q000601:surgery*; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D007365:Intercellular Junctions / Q000187:drug effects; D007429:Intraocular Pressure / Q000187:drug effects; D007668:Kidney / Q000166:cytology / Q000187:drug effects; D053685:Laser Therapy; D053844:Lasers, Solid-State; D008565:Membrane Proteins / Q000235:genetics / Q000494:pharmacology; D010750:Phosphoproteins / Q000235:genetics / Q000494:pharmacology; D011453:Prostaglandins / Q000494:pharmacology / Q000627:therapeutic use*; D011785:Quality Assurance, Health Care; D012189:Retrospective Studies; D012590:Sclera / Q000166:cytology; D014129:Trabecular Meshwork / Q000166:cytology; D014130:Trabeculectomy; D014162:Transfection; D016896:Treatment Outcome; D062826:Zonula Occludens-1 Protein
D017077:Culture Media, Conditioned; D008565:Membrane Proteins; D010750:Phosphoproteins; D011453:Prostaglandins; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein; D049452:Green Fluorescent Proteins