H-7 effect on outflow facility after trabecular obstruction following long-term echothiophate treatment in monkeys

Invest Ophthalmol Vis Sci. 2004 Aug;45(8):2732-6. doi: 10.1167/iovs.04-0083.

Abstract

Purpose: 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / therapeutic use*
  • Accommodation, Ocular / drug effects
  • Animals
  • Aqueous Humor / metabolism*
  • Cholinesterase Inhibitors / toxicity
  • Disease Models, Animal
  • Echothiophate Iodide / toxicity
  • Female
  • Intraocular Pressure / drug effects*
  • Macaca fascicularis
  • Male
  • Ocular Hypertension / chemically induced
  • Ocular Hypertension / drug therapy*
  • Ocular Hypertension / metabolism
  • Refraction, Ocular
  • Trabecular Meshwork / drug effects*
  • Trabecular Meshwork / metabolism

Substances

  • Cholinesterase Inhibitors
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • Echothiophate Iodide