Age-related loss of accommodation in rhesus monkeys is associated with an age-related increase in lens stiffness

Abstract

Purpose: It is generally agreed that presbyopia in humans is caused by an age-related increase in lens stiffness. Rhesus monkeys develop presbyopia with a similar relative age-course as humans and are used as an animal model for human presbyopia, although prior studies have suggested differences in the aetiology of presbyopia between humans and monkeys. Here, the age-related loss of accommodation from in vivo and in vitro experiments is correlated with the stiffness of the same lenses to ascertain the relationship between presbyopia and lens stiffness in rhesus monkeys.

Methods: Experiments were performed on 10 iridectomized rhesus monkeys aged between 10 and 25 years. Accommodation was stimulated with intravenous pilocarpine and refraction measured with a Hartinger and infrared photorefraction and accommodative changes in lens diameter measured with slit-lamp videography. After euthanasia, one eye each from nine monkeys was used for mechanical stretching experiments in which changes in lens focal length and lens diameter were measured as a function of the applied radial stretch. Lenses were then isolated and squeezed in six 100 µm steps while measuring the applied force.

Results: In vivo accommodative amplitudes decreased linearly with age (r² = 0.9097; p < 0.001) and accommodative change in lens diameter decreased linearly with age (r² = 0.8097; p < 0.001). With mechanical stretching the lens power and lens diameter curves for each lens plateaued and the maximum changes in lens power and diameter from all lenses decreased linearly with age (r² = 0.8805; p < 0.001 and r² = 0.62; p < 0.001, respectively). Maximum gram force from squeezing lenses increased exponentially with age (f = 0.0408 * 1.1658^age p < 0.001). In vivo accommodation, in vivo accommodative change in lens diameter and in vitro change in lens focal length were significantly exponentially related (p < 0.001) to the maximum gram force from squeezing the lenses.

Conclusions: In rhesus monkeys accommodation is lost with increasing age, lens stiffness increases exponentially with age, in vitro accommodation is not limited by ciliary muscle function and the magnitudes of in vivo ocular and in vitro lenticular accommodative changes are related to lens stiffness. These results demonstrate that in rhesus monkeys, as in humans, presbyopia is caused by a progressive age-related increase in lens stiffness.

Keywords: 404 accommodation • 653 presbyopia