Effects of pharmacologically manipulated amplitude and starting point on edinger-westphal-stimulated accommodative dynamics in rhesus monkeys.

Accommodation is a dynamic process that allows the eye to focus on objects at different distances. In humans, accommodation can occur reflexively1 and by a voluntary effort to focus on a near object.2,3 Dynamic accommodation can be produced in anesthetized rhesus monkeys by stimulating the Edinger-Westphal (EW) nucleus.4–6 Dynamics of far-to-near (accommodative) or near-to-far (disaccommodative) responses can be quantified by velocity and acceleration characteristics.3,5,7 The relationship between amplitude and peak velocity of a response is known as a main sequence.8 Dynamic analysis of EW-stimulated accommodation in anesthetized adolescent rhesus monkeys shows that the main sequence increases linearly over the full range for accommodation and disaccommodation, with disaccommodation occurring progressively faster than accommodation.5 With supramaximal current stimulation (i.e., a current amplitude greater than required to achieve maximum accommodation), peak velocity of accommodation increases further without a further increase in response amplitude. Peak velocity of disaccommodation does not increase further but depends on the disaccommodative response amplitude.9 Several studies have examined accommodative dynamics in humans. In young subjects, the time constant of accommodation and the peak velocity of disaccommodation back to baseline increase linearly with response amplitude.3,10 Peak velocity of accommodation increases at low response amplitudes, saturates at higher amplitudes,3 and is slower than for disaccommodation.2,11 The dynamics of accommodation and disaccommodation are influenced by response amplitude and starting point.12,13 Therefore, response amplitude, starting configuration of the accommodative structures, associated biomechanical characteristics, and neuromuscular activity may play a role in the dynamics of the response. In rhesus monkeys, muscarinic agonists such as pilocarpine and carbachol cause a progressive ciliary muscle contraction, a myopic refractive shift, and, hence, a decrease in EW-stimulated accommodative response amplitude.9,14 Muscarinic antagonists such as atropine and pirenzepine cause cycloplegia because the ciliary muscle neuromuscular receptors are blocked. Pharmacologic stimulation can therefore be used in monkeys to alter refractive state, EW-stimulated accommodative response amplitude, and starting point. EW stimulation after pilocarpine allows evaluation of the dynamic accommodative response as the amplitude decreases with the pilocarpine-induced myopic shift and from more proximal starting points. EW stimulation after atropine allows evaluation of the dynamic accommodative response as the maximum amplitude decreases because of cycloplegia. Atropine and pilocarpine change maximum response amplitude through different actions at the ciliary neuromuscular junctions without affecting the EW neurons. This allows determination of the effects that receptor blockage, partial muscle stimulation, shift in starting point, and reduced response amplitude have on the accommodative response dynamics. Studies of agonists and antagonists have used similar techniques to evaluate their effects on accommodative dynamics in monkeys.9,14,15 Adolescent rhesus monkeys have high pharmacologically9,16,17 and centrally stimulated accommodative amplitudes.5,18,19 The accommodative mechanism20,21 and anterior segment anatomy22,23 are similar to those in humans. The age-related loss of accommodative amplitude, when adjusted for lifespan, is similar to the progression of presbyopia in humans24 and has a similar etiology.25,26 Rhesus monkeys are widely recognized as an ideal animal model for studies of human accommodation and presbyopia.16,17,22,24–27 In this study, pilocarpine and atropine were used to alter response amplitude and starting point in adolescent rhesus monkeys to study the effects on accommodative and disaccommodative dynamics during centrally stimulated accommodation.