Age-Related Loss of Ciliary Muscle Contractility

In primary open-angle glaucoma, eye pressure is elevated because of obstructed drainage of fluid 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 for 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 at least in part consequent to an age-related loss of ciliary muscle function.

Hypothesis

Our hypothesis is that a loss in ciliary muscle contractility with age may be directly associated with the increased incidence of glaucoma with age. We think that this inability of the ciliary muscle to contract as a monkey (or human) gets older is partly due to changes in its attachments to the back of the eye, rather than just to changes in the muscle itself or to the presence of the lens.

Specific Aims

We plan to study the contraction of the ciliary muscle in living animals and in isolation. This will allow a more detailed analysis of muscle function in the presence and absence of its normal attachments and surrounding eye tissues, which may also influence contraction. One component of our project involves videotaping and image analysis of the ciliary muscle in living rhesus monkeys of different ages. In these animals, we will measure the rate of muscle contraction, the amount of muscle movement, and the relationship of the muscle to the lens and other structures in the eye before, during and after contraction. By surgically manipulating these structures, using similar procedures to those used in human cataract surgery, we can also evaluate the influence the lens and its structural membranes have on ciliary muscle movement. Additionally, movement of the isolated ciliary muscle will be assessed in post-mortem monkey eyes of different ages. The contractile force induced by drugs which are currently used to treat glaucoma, as well as by new experimental drugs, will be analyzed. New drugs are currently being developed that may be better at treating glaucoma without producing many of the side-effects associated with these types of medications. In our experimental system, we may be able to identify drugs which will contract the portion of the muscle responsible for controlling the outflow channels without producing the side effect of near-sightedness, caused by involuntary accommodation. Thus far, with the help of AHAF funding, 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 monkey. We have also 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. Microscopic evaluation of drug-induced ciliary muscle movement in post-mortem eyes indicated that with age, stiffening of the posterior attachment of the muscle restricts its mobility.

Long-Term Goals

Further studies will attempt to directly correlate ciliary muscle movement with ocular fluid drainage in individual animals of different ages to provide more direct support for the hypothesis, and will also attempt to determine whether the accommodative and outflow components of ciliary muscle contraction can be activated separately by more specific drugs than are currently available. 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, 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.