Pharmacologic disruption of Schlemm's canal cells and outflow facility in anterior segments of human eyes.
OBJECTIVE
To determine the effect of disruption of Schlemm's canal cells on outflow facility. Pharmacologic agents that weaken the cytoskeleton or interfere with integrin binding may allow targeted disruption of the cells lining Schlemm's canal because of the transmural pressure gradient the cells face as aqueous passes into the canal.


METHODS
Anterior segments of human eyes were placed in perfusion organ culture, and either single or sequential doses of H-7 or RGD peptide were added. Fellow eyes received vehicle or RGE peptide. Eyes were fixed and examined by light and electron microscopy.


RESULTS
Both agents caused a partial loss of the endothelial lining of Schlemm's canal cells without disruption of trabecular cells in other regions. H-7 significantly increased outflow facility after single or sequential doses, with moderate cell loss of both the inner and outer wall canal cells: 20.0% +/- 10.5% of the width of the canal versus 5.2% +/- 3.7% in control meshworks (P = 0.05). No significant correlation between the amount of canal cell loss and outflow facility was found. RGD was associated with a variable loss of canal cells but did not change outflow facility.


CONCLUSIONS
Pharmacologic disruption of Schlemm's canal cells appears possible. H-7 increased outflow facility, causing a partial loss of the endothelial lining of Schlemm's canal. A simple relationship between canal cells and outflow facility was not found; canal cells probably interact with the extracellular matrix in influencing outflow facility.
Bahler
Cindy K
CK
Department of Ophthalmology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
Hann
Cheryl R
CR
Fautsch
Michael P
MP
Johnson
Douglas H
DH
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001082:Aqueous Humor / Q000378:metabolism*; D002470:Cell Survival; D042783:Endothelial Cells / Q000187:drug effects* / Q000648:ultrastructure; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects; D008875:Middle Aged; D009842:Oligopeptides / Q000494:pharmacology*; D009924:Organ Culture Techniques; D014129:Trabecular Meshwork / Q000187:drug effects* / Q000648:ultrastructure
D004791:Enzyme Inhibitors; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine