Anticholinesterase-induced cholinergic subsensitivity in primate accommodative mechanism

Area of Science:

• Ophthalmology
• Neuroscience
• Pharmacology

Background:

• Echothiophate iodide is an organophosphate used to treat certain eye conditions.
• Organophosphates are known to inhibit acetylcholinesterase, potentially affecting cholinergic signaling.
• The ciliary muscle's accommodative function relies on cholinergic neurotransmission.

Purpose of the Study:

• To investigate the effects of chronic topical echothiophate iodide administration on the cholinergic sensitivity of the ciliary muscle in cynomolgus monkeys.
• To assess the reversibility of any induced changes in accommodative response after drug cessation.

Main Methods:

• Cynomolgus monkeys were treated with topical echothiophate iodide for several months.
• Accommodative responses to pilocarpine (topical and intramuscular) were measured before and after cholinergic blockade.
• Recovery of accommodative response was monitored after discontinuing echothiophate iodide treatment.

Main Results:

• Echothiophate iodide treatment markedly reduced accommodative responses to both topical and intramuscular pilocarpine.
• Even high doses of pilocarpine elicited minimal response in treated eyes compared to controls.
• Within seven weeks of cessation, accommodative sensitivity to pilocarpine partially recovered (30-50% of control levels).

Conclusions:

• Chronic topical echothiophate iodide induces cholinergic subsensitivity in the ciliary muscle.
• This subsensitivity is associated with impaired accommodative function.
• The observed changes are at least partially reversible upon drug withdrawal.