Glaucoma Research

Glaucoma occurs as the result of a disturbance in fluid flow through the eye that causes an increased pressure to occur inside the globe. Just as there are many aspects to glaucoma, our research addresses some of these aspects such as, What are the underlying causes of the disease? What are the forces that move fluid into the eye? What regulates fluid outflow from the eye?, and How can new drugs be developed to regulate either fluid inflow or fluid outflow? Our goal is to discern how various factors can influence each of these processes and how they can be manipulated to regulate eye pressure. Much of the current medical treatment for glaucoma tends to be rather empirical, and the basis for the use of several drugs has little basis in scientific understanding. Our approach is to understand the basic systems that are responsible for fluid entry into, and exit from, the eye and then attempt to modify these systems. On the inflow side, fluid enters the eye through the ciliary epithelium which is a two-cell layer thick membrane located behind the iris. Each layer is thought to have a different role to play in fluid entry, but this has not been determined. Using very fine glass electrodes of which only the very tips are placed inside a cell to measure its voltage, we have made considerable progress in understanding how the whole tissue functions. We have made great strides in understanding how different chemicals contribute to this voltage, and how different drugs alter the rate of entry or loss of the chemicals from the cells. Now, using cells grown in tissue culture, we will study the behavior of individual cell layers and test the hypothesis that the cell layers are different in terms of their contribution to fluid entry into the eye. From these results we will be able to learn how to modify these cells to reduce the flow of fluid entry and hence reduce eye pressure. Through understanding of the basic cellular mechanisms we can expand our insight into how these cells function, and how they can be regulated. One of our major areas of interest has concerned the involvement of hydrogen peroxide as a causative factor in glaucoma. The aqueous humor is one of the only places in the body where a high concentration of hydrogen peroxide exists. This chemical can alter the characteristics of membranes that cause cell damage and, we believe, aging. Glaucoma occurs more frequently with increased age, and there is considerable evidence that many of the changes seen in the glaucomatous eye are similar to those occurring in an aged eye. Our hypothesis is that the presence of hydrogen peroxide in eye fluids plays an important role in glaucoma. We have already shown that, in several tissues in the front portion of the eye, one of the major enzymes that breaks down hydrogen peroxide to water decreases with increasing age. This in turn leads to an extension of the time that hydrogen peroxide stays in the eye, and hence damage can occur. We have been working intensively on examination of how hydrogen peroxide in the aqueous humor (the fluid that bathes the tissues at the front of the eye) is regulated by different enzymes. We plan to test this hypothesis further by using cells from the area where fluid drains from the eye (the trabecular meshwork), and studying the effects of hydrogen peroxide on their function. Cells of the trabecular meshwork will be placed in tissue culture and exposed to hydrogen peroxide under a variety of conditions. These situations would be such as after slowing down one of the enzymes that normally protects the cells against peroxides (in order to study which enzyme is more important), or after treatment with other antioxidants (such as beta-carotene) in order to study the degree of protection offered by these latter agents either alone or in combination with others. In this way we will find out much more about how the eye tissues can be protected and, hopefully, devise preventive measures that may protect the eye from changes. We have already been able to grow trabecular meshwork cells in culture under normal conditions during the past year. Turning to treatments for glaucoma, we are examining new chemicals obtained from plants as well as other synthetic drugs to determine how efficient they are at reducing eye pressure. One extract is from a plant material that reduces eye pressure for several days in laboratory animals after only one eye drop. The active ingredient has been identified and we are examining the longer term effects of this chemical to determine if there are any deleterious effects. We are also looking at different aspects of eye physiology to see how the drug works and how the material causes such a protracted fall in eye pressure. This is a very exciting finding as it offers the potential of a new approach to the regulation of eye pressure. Because this agent works as a topical drop and its chemical structure is relatively simple, it will be easy to modify in order to enhance desirable characteristics or reduce undesirable ones. Other extracts of other plants, including marihuana, are also being tested to determine how they cause the long fall in eye pressure, and where they act to cause this pressure fall. Here also, the long fall in intraocular pressure over several days opens up the possibility of identifying new ways of reducing eye pressure. There is a need for new medical treatment in glaucoma and we are hopeful that at least one of the drugs undergoing testing at present in animals will one day, in some form, be available for glaucoma treatment. Some of these new drugs appear to act in unique ways to reduce eye pressure, and thus may offer new approaches for therapy. Our aims, therefore, are focused on these three main approaches to glaucoma; an understanding of how fluid enters the eye and how it can be regulated, knowledge of how hydrogen peroxide can influence the outflow pathways for fluid exit from the eye, and how new drugs influence eye pressure. Our long-term goals are to further understand each of these areas. Successful achievement of these goals will lead to more successful treatment of this disease, as well as the introduction of preventive measures, and a more fundamental understanding of the processes leading to the development of glaucoma.