Prostaglandins increase trabecular meshwork outflow facility in cultured human anterior segments.
OBJECTIVE
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.


METHODS
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.
Bahler
Cindy K
CK
Department of Ophthalmology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
Howell
Kyle G
KG
Hann
Cheryl R
CR
Fautsch
Michael P
MP
Johnson
Douglas H
DH
D000368:Aged; D000369:Aged, 80 and over; D000527:Alprostadil / Q000494:pharmacology*; D000869:Anterior Eye Segment / Q000187:drug effects / Q000201:enzymology; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001082:Aqueous Humor / Q000378:metabolism*; D015153:Blotting, Western; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D000077338:Latanoprost; D020782:Matrix Metalloproteinases / Q000378:metabolism; D009924:Organ Culture Techniques; D011461:Prostaglandins F, Synthetic / Q000494:pharmacology*; D012590:Sclera / Q000502:physiology; D014129:Trabecular Meshwork / Q000187:drug effects* / Q000201:enzymology
D000959:Antihypertensive Agents; D011461:Prostaglandins F, Synthetic; D000077338:Latanoprost; D020782:Matrix Metalloproteinases; D000527:Alprostadil