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Many studies have used pilocarpine to stimulate accommodation in both humans and monkeys. However, the concentrations of pilocarpine used and the methods of administration vary.

In this study, three different methods of pilocarpine administration are evaluated for their effectiveness in stimulating accommodation in rhesus monkeys. Experiments were performed in 17 iridectomized, anesthetized rhesus monkeys aged 4—16 years. Alternatively, while supine, 10—12 drops of pilocarpine were maintained on the cornea in a scleral cup for 5 min. Refraction measurements were begun 5 min after the second application of pilocarpine and continued for at least Topical pilocarpine in clitoris min after initial administration until no Topical pilocarpine in clitoris change in refraction occurred.

In intravenous experiments, pilocarpine was Topical pilocarpine in clitoris either as boluses ranging from 0. Topically applied pilocarpine produced 3. IV boluses of pilocarpine Aunt judys sherry older near maximal levels of accommodation at least ten times faster than topical methods. Doses effective for producing maximum accommodation ranged from 0.

IV pilocarpine boluses caused an anterior movement of the anterior lens surface, a posterior movement of Topical pilocarpine in clitoris posterior lens surface, and a slight net anterior movement of the entire lens.

Considerable variability in response amplitude occurred and maximum accommodative amplitude was rarely achieved with topical application of a variety of concentrations of commercially available pilocarpine. Intravenous infusion of pilocarpine was a rapid and reliable method of producing a nearly maximal accommodative response and maintaining accommodation when desired. Accommodation is a dioptric change in optical power of the eye to change focus from far to near.

The mechanism of accommodation has been studied extensively in both humans and monkeys. Rhesus monkeys are a long and widely used animal model for human accommodation and presbyopia because rhesus monkeys have high accommodative amplitudes Bito et al.

Age related changes in the rhesus monkey eye are similar in all respects to that in humans and rhesus monkeys are an excellent animal model for studies of human accommodation and presbyopia Koretz et al. Other animal species either do not accommodate or if they do, they have accommodative mechanisms and accommodative anatomy quite unlike that of the human eye and therefore cannot be used for studies of accommodation in general and are inappropriate animal models for the study of human accommodation Glasser, ; Glasser et al.

Mammals such as mice and pigs have extremely diminutive ciliary muscles Samuelson, and considerably more spherical lenses Campbell and Hughes, ; Vakkur and Bishop, ; Vilupuru and Glasser, than primates rendering them unsuitable as animal models of human accommodation.

No animal species other than primates have an accommodative mechanism similar to humans, an accommodative anatomy similar to humans and develop Topical pilocarpine in clitoris with the same relative age course as humans.

The applicability of rhesus monkeys to humans with regard to accommodation and presbyopia and Topical pilocarpine in clitoris absence of other appropriate animal models means that rhesus monkeys are the only animal model in which to study the mechanisms of accommodation and presbyopia and experimental surgical procedures to restore accommodation to Topical pilocarpine in clitoris presbyopic eye Koopmans et al. The study of aspects of accommodation and presbyopia in rhesus monkeys relies on the ability to induce accommodation.

While this can be accomplished behaviorally in awake monkeys Bossong et al. It is therefore necessary to be able to induce accommodation in anesthetized monkeys in a reliable and reproducible manner. While this can be accomplished with Edinger-Westphal EW stimulation of the brain, for example, this complex neuro-physiological procedure is not widely used or generally accessible and further, EW stimulation necessarily results in a rapid and strong convergence eye movement because of the proximity of the EW nucleus to the ocular-motor nucleus in the brain.

Therefore, this study was undertaken to establish how well intravenous i. The ability to achieve this will permit other ocular imaging techniques to be used on rhesus monkeys that may otherwise be compromised by eye movements. This may further help to elucidate aspects of the accommodative mechanism and the cause of presbyopia to facilitate the growing effort directed at restoring the accommodative ability to the presbyopic eye. In conscious humans, accommodation is typically stimulated either with a visual stimulus or pharmacologically with topically applied pilocarpine.

Accommodation has been studied in anesthetized monkeys by stimulating the Edinger-Westphal EW nucleus in the brain Crawford et al. Carbachol and pilocarpine are cholinergic agonists which bind at the cholinergic receptors to cause an accommodative response by directly stimulating a contraction of the ciliary muscle.

A variety of different methods have been used to apply drugs to the eye to induce accommodation in anesthetized monkeys including: topical application of eye-drops Koopmans et al. Application of commercially available muscarinic agonists to the Topical pilocarpine in clitoris may Topical pilocarpine in clitoris the most readily available method of stimulating accommodation.

Topical administration of carbachol or pilocarpine can be problematic for a number of reasons. This can include low Topical pilocarpine in clitoris of the drugs through the cornea and systemic effects when high concentrations are used Asseff et al. Efforts have been made to ensure that the drug enters the eye only through the cornea and does not come in contact with the limbus which may lead to a systemic reaction Rohen et al.

In humans, topical pilocarpine induced accommodative Topical pilocarpine in clitoris have been shown to vary among similar aged individuals, dependent on iris color and absorption of the drug by the ocular pigment epithelium and the amplitudes achieved do not always compare well with maximal accommodative response amplitudes elicited with visual stimulation Ostrin and Glasser, ; Wold et al.

The time-course of the topically induced accommodative response is slow and variable and the accommodative response achieved will therefore depend on the time after topical application at which the response is measured. Although topical application of pilocarpine is relatively widely used to stimulate accommodation in anesthetized monkeys, no study has systematically evaluated the efficacy of stimulating accommodation in monkeys in this way, the effects of different concentrations, the time-course of the accommodative response or the amplitudes achieved.

This produced a stable level of accommodation which was assumed to be the maximal accommodative response amplitude Wendt et al. Using this method, pilocarpine appears to penetrate the cornea at a similar rate to topical pilocarpine drops. However, constant exposure to the pilocarpine ensures that the eye achieves a stable maximum level of accommodation.

The accommodative response achieved in this way is slow. This slow response time means that only a single stimulation can be performed per experiment using this method. Other drawbacks of constant perfusion derive from the presence of the perfusion lens in front of the eye.

Many commonly used accommodation measurement techniques cannot be used in conjunction with the perfusion lens and the slow response times involved. These include goniovideography, refractometry, intraocular pressure measurements, magnetic resonance imaging, and continuous ultrasound biometry. Finally, when imaging methods can be used in conjunction with the perfusion lens Glasser et al. In addition to topical application, pilocarpine has been used to stimulate accommodation in anesthetized monkeys by intramuscular i.

However, high doses can produce systemic side effects in addition to a paradoxical reduction in accommodative amplitude due to a systemic decrease in blood pressure Tornqvist, Protective i. Although i. Studies in monkeys have shown that carbachol iontophoresis induced accommodation differs from EW stimulated accommodation Ostrin and Glasser, Similarly, in humans, accommodation stimulated with topical pilocarpine differs from the visual stimulus induced response Koeppl et al.

In particular, pharmacological induced contraction of the ciliary muscle produces a net forward movement of the lens that does not appear to occur when the stimulus to accommodate comes from the brain Bolz Topical pilocarpine in clitoris al.

This difference could be because topical drug stimulation results in far higher Topical pilocarpine in clitoris of drug reaching the ciliary neuron-muscle receptors to cause a supra-maximal contraction of the muscle compared Topical pilocarpine in clitoris the amount of neurotransmitter release at neuromuscular junctions when the stimulus to accommodate comes from the brain Crawford et al. Intravenous pilocarpine delivery rates and concentrations can be rigorously controlled relative to topical drug administration and just-sufficient doses, as opposed to supra-maximal doses, can be administered to avoid side effects.

Therefore, it is possible that i. This aspect of the i. Here, several methods of producing a pilocarpine stimulated accommodative response in rhesus monkeys Topical pilocarpine in clitoris studied Topical pilocarpine in clitoris evaluate their ability to produce a rapid, repeatable, and sustained accommodative response.

Prior studies have not documented a method to achieve a rapid and a sustained, natural accommodative response in monkey eyes with pharmacological stimulation. The methods considered in this study were constant topical administration with a perfusion lens to maintain pilocarpine solution in contact with the cornea, topical application of pilocarpine eye drops of various concentrations, and bolus and constant i. Experiments were performed on the eyes of 17 rhesus monkeys Macaca mulatta ranging in age from 4 to 16 years.

Each monkey had previously undergone total iridectomy and was housed in rooms away from bright lighting. Joseph, MO. In addition to propofol, some monkeys received 0. In these cases, monkeys were intubated following propofol anesthesia and were respirated either periodically, manually with an Ambu bag or constantly with a Harvard pump with O 2 at a Topical pilocarpine in clitoris of 1 L per minute. After these experiments, medetomidine was reversed with 0.

Due to logistical reasons, not all of the 17 monkeys were used in each type of experiment. Table 1 shows the different monkeys and the experiments in which they were used. Table showing monkeys and the experiments performed.

The age of the monkey shows the age range from the first experiment to the last experiment performed. The numbers in the table indicate the number of times the monkey was used in a particular experiment. Static measurements of accommodation were made using a Hartinger coincidence refractometer Carl Zeiss Meditec, Jena, Germany. Photorefraction was used for dynamic accommodation measurements similar to that described previously Vilupuru and Glasser, The camera was fixed at a distance of 0.

Video images were recorded to digital videotape and Topical pilocarpine in clitoris analyzed on-line in a Matlab The MathWorks, Inc. Low frequency recordings were used because of the long duration of the experiments. To convert the measured slopes to accommodation, a calibration was initially performed with trial lenses of known power held in front of the eye.

For each trial lens power, 30 video frames were analyzed and a mean calculated. Topical pilocarpine in clitoris mean slopes obtained with each lens were used to develop a calibration curve for all subsequent measurements. On the contra-lateral eye, dynamic biometric anterior chamber depth and lens thickness accommodative changes were measured with continuous high-resolution A-scan ultrasound biometry Topical pilocarpine in clitoris Beers and van der Heijde, ; Vilupuru and Glasser, Biometric measurements were recorded to computer at 0.

The transducer was aligned along the optical axis of the eye with a manipulator and maintained in contact with the cornea through ultrasound transmission gel Liquasonic Ultrasound gel; Chester Laboratories, Inc. In the initial topical pilocarpine experiments, monkeys were prone on a table with the head in a head holder, upright and facing forward.

A clear, plano contact lens was placed on the cornea to prevent dehydration and preserve optical quality. The baseline refraction was measured with the Hartinger. The contact lens was then removed and either saline or pilocarpine solution was maintained in contact with the cornea in a specially designed perfusion lens which was placed over the cornea and held in place beneath the eyelid Wendt et al.

As the eye accommodates, equatorial lens diameter decreases linearly with accommodation. Lens diameter was therefore used as a measure of the accommodative progression Glasser et al. Images of the lens diameter in the iridectomized eyes were captured through the perfusion lens once every 10 seconds by a video camera attached to a slit-lamp microscope.

Lens diameters were measured using a custom written Matlab program. Lens diameter measurements proceeded until no further decrease in lens diameter was observed in the on-line recordings. Since lens diameter has been shown to be linearly related to accommodation over the full range of the accommodative response Glasser et al.

The time required to achieve a stable minimum lens diameter varied from 30 min to an hour. The perfusion lens was then removed from the eye and the contact lens was placed back on the cornea. Finally, Hartinger measurements were made to determine Topical pilocarpine in clitoris accommodative change in refraction. In the topical pilocarpine experiments, the monkeys were held upright and facing forward in a head holder and baseline refraction was measured with a Hartinger coincidence refractometer with and without a contact lens.

Monkeys received 2 or 4 drops in two applications or 6 drops in three applications over a 5-min period with the eyelids closed between applications.


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