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.
Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, 53792, USA.
B'Ann T
BT
Gabelt
Elizabeth A
EA
Hennes
Jennifer L
JL
Seeman
Baohe
B
Tian
Paul L
PL
Kaufman
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