H-7 effect on outflow facility after trabecular obstruction following long-term echothiophate treatment in monkeys.
OBJECTIVE
To determine whether H-7 can enhance outflow facility after trabecular meshwork obstruction by extracellular material that accumulates after long-term treatment of monkeys with the cholinesterase inhibitor echothiophate iodide (ECHO).


METHODS
Cynomolgus monkeys were treated topically with 150 microg ECHO in one (n = 4 eyes) or both (n = 8 eyes) eyes for up to 48 weeks. Accommodation response to topical pilocarpine was monitored periodically. Outflow facility response to H-7 was measured by two-level constant pressure perfusion on three or four different occasions after intraocular pressure was elevated for 12 to 18 weeks.


RESULTS
Long-term treatment with ECHO decreased the accommodative response to pilocarpine and increased intraocular pressure, as has been reported. Baseline outflow facility was decreased by 46% +/- 7% (n = 12, P < 0.001). H-7 partially restored baseline outflow facility measured during subsequent perfusions while ECHO treatment was continued. Concurrent H-7 enhanced outflow facility by 73% +/- 18% (n = 12, P < 0.005) beyond the same-day baseline in ECHO-treated eyes. Cessation of ECHO treatment further restored baseline outflow facility, and the outflow facility response to H-7.


CONCLUSIONS
H-7 can enhance OF in the presence of trabecular obstruction produced by long-term ECHO treatment. This suggests that H-7 may be useful in treating glaucoma, even in the presence of accumulated plaque material that has been described previously.
Gabelt
B'Ann T
BT
Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, 53792, USA.
Hennes
Elizabeth A
EA
Seeman
Jennifer L
JL
Tian
Baohe
B
Kaufman
Paul L
PL
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000627:therapeutic use*; D000065:Accommodation, Ocular / Q000187:drug effects; D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000633:toxicity; D004195:Disease Models, Animal; D004456:Echothiophate Iodide / Q000633:toxicity; D005260:Female; D007429:Intraocular Pressure / Q000187:drug effects*; D008252:Macaca fascicularis; D008297:Male; D009798:Ocular Hypertension / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D012029:Refraction, Ocular; D014129:Trabecular Meshwork / Q000187:drug effects* / Q000378:metabolism
D002800:Cholinesterase Inhibitors; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D004456:Echothiophate Iodide