Atropine reduces but does not eliminate the age-related decline in perfusion outflow facility in monkeys

Accommodative amplitude and outflow facility decline with age in rhesus monkeys and humans. In monkeys, there is an age-related reduction in ciliary muscle (CM) mobility due to stiffening of its posterior and outer attachments. Since the CM inserts into the trabecular meshwork (TM) and CM contraction deforms the TM so as to increase outflow facility, we asked whether the age-related decline in outflow facility observed in anesthetized monkeys is consequent to the age-related reduction in CM mobility. One eye of 19 pentobarbital-anesthetized rhesus monkeys aged 4-24 years underwent 2-level constant pressure perfusion of the anterior chamber (AC) for 40 min to measure baseline total outflow facility. Both eyes then received 100 micrograms of atropine, given topically to the central cornea. The AC of the second eye was cannulated 40 min after atropine treatment. Facility was measured simultaneously in both eyes for 40 min beginning 45 min after atropine treatment. Baseline facility declined with age by -0.0160 +/- 0.0059 microliters min-1 mmHg-1 yr-1 (P = 0.009). The average facility at baseline was approximately 50% higher in the youngest (ages 4-10 years) compared to the oldest (ages 21-25 years) animals (P < or = 0.03). Following atropine facility decreased by approximately 25% in the youngest monkeys (N.S.), but not at all in the oldest animals when compared to baseline. Thus, the age-related facility decline persisted after atropine in both eyes, but was not as dramatic as prior to atropine (-0.0092 +/- 0.0050 [P < or = 0.09] and -0.0078 +/- 0.0044 [P < or = 0.10] microliter min-1 mmHg-1 yr-1 respectively). Apparently, atropine inhibits facility-relevant anesthetic-induced ciliary muscle tone to a greater extent in younger than in older monkeys, presumably because stiffening of the posterior and outer attachments of the CM in the older animals has already reduced its ability to move and thereby deform the TM. The inability of atropine to completely eliminate the age-related facility decline indicates the presence of atropine-independent, facility-relevant age-dependent changes in the TM itself, such as loss of cells or build-up of extracellular material.