Age-Related Loss of Ciliary Muscle Contractility

In primary open-angle glaucoma, eye pressure is elevated because of obstructed fluid drainage from inside the eye. The cause of the obstruction is unknown but is associated with aging. Recently, we found that in rhesus monkeys, the small ciliary muscle inside the eye responsible for accommodation (focusing near vision) loses its function with age. This muscle is also connected to and assists the tissues draining fluid from the eye. Since both humans and monkeys lose the ability to focus near vision with age, it seems likely that in humans, ciliary muscle function also declines with age. Therefore, it seems possible that the development of glaucoma in humans might be consequent to an age-related loss of ciliary muscle function. Our project involves videotaping and analyzing the degree of ciliary muscle contraction in rhesus monkeys of different ages to see if the loss of function is accompanied by increased resistance to ocular fluid drainage, which we will also measure in those same animals. Additionally, movement of the muscle in response to contraction-inducing antiglaucoma drugs will be assessed microscopically in postmortem monkey and human eyes of different ages. Collectively, the findings could redirect our search for the underlying cause of primary open-angle glaucoma from the drainage tissues themselves to the ciliary muscle and the elastic tissues to which it is connected. Thus far, we have perfected the techniques for stimulating and videotaping movement of the ciliary muscle and have demonstrated the age-related loss of muscle function in the living monkey. Furthermore, we have shown that the loss of accommodative function is highly correlated with an increase in resistance to ocular fluid drainage and a decreased responsiveness to drugs which enhance fluid drainage by directly stimulating the ciliary muscle, and that all of these functional changes are highly correlated with aging. Finally, we have developed the microscopic techniques needed to evaluate drug-induced ciliary muscle movement in post-mortem eyes, and have preliminarily found that with age, stiffening of the posterior attachment of the muscle restricts its mobility. Thus, the hypothesis that an age-related decrease in ciliary muscle function impairs the ocular fluid drainage apparatus is consistent with our data and with the hypothesis that impaired ciliary muscle function is a predisposing factor to the development of primary open-angle glaucoma. Further studies will attempt to directly correlate ciliary muscle movement with ocular fluid drainage in animals of different ages to provide more direct support for the hypothesis.