Laboratory Studies in Glaucoma

In all individuals, the pathways which the aqueous humor (the clear fluid that nourishes the front part of the eye) takes to leave the eye offer some resistance to the outflow of aqueous humor. If this were not the case, the cornea would lose its convex shape, and thus, it’s important refractive role in focusing images on the retina. In POAG the pathways are somehow “clogged” and the resistance to aqueous humor flow becomes too great. The increased resistance causes the eye pressure to increase, ultimately leading to irreversible damage to the optic nerve. One of the reasons that POAG has been difficult to study is that no one really knows what causes the outflow pathway tissues to become “clogged” as there is no obvious pathology that can be seen microscopically. Further, although scientists are fairly certain about where the resistance lies in normal eyes, there is no clear understanding of what actually comprises the resistance. Therefore, in order to understand the cause of primary open angle glaucoma (POAG) it is necessary to understand what the cells that line the aqueous outflow pathways “do”. One way of trying to decide what the cells “do” is to try to understand how various drugs can affect their function. Ophthalmologists take advantage of the fact that certain classes of drugs are known to lower outflow resistance (and therefore eye pressure) and they use these drugs to treat glaucoma. However, even though certain drugs can lower eye pressure by changing the pathway’s resistance, very little is actually known about how the resistance is changed. The ultimate answer to this question is not simple as it requires the expertise of scientists from many different fields to study the tissue’s structure, its biochemistry, and its physiology. During the past year the members of our group have moved toward a greater understanding of what actually comprises the outflow resistance and how it can be altered. Microscopic studies have investigated the tissue structure finding that the structure of the cell layer thought to be an important barrier to fluid movement is really no different in normal eyes than it is in eyes from individuals with glaucoma. This preliminary finding is important because the study was done under lifelike conditions (unlike previous studies), and thus, clears up a controversy over whether or not this cell layer is structurally different in eyes with glaucoma. Another finding this year is that the resistance to aqueous outflow in normal eyes is correlated to the number of “holes” visible in a certain portion of the outflow pathway. This finding may hold a clue to what comprises resistance in normal eyes. In other studies, two new classes of drugs have been found to decrease the outflow resistance in monkey eyes in vivo and/or human eyes in vitro. These findings are important as they may point to new types of therapeutic intervention and they provide more clues to how the outflow pathway cells are able to alter the outflow resistance. The cells of the aqueous outflow pathway are nourished by aqueous humor. Therefore, it is very important to know what the composition of the aqueous humor is, as it is possible that any deficiencies in its composition or any toxins that might be present would cause the cells to become damaged. During the past year our laboratory has made further progress in characterizing the composition of aqueous humor proteins. An interesting finding is the identification of a protein that is also found in the cornea which may play an important role in the regulation of outflow resistance. Further studies have successfully employed the sophisticated technology of nuclear magnetic resonance to measure biochemical pathways. This is a real advantage over most biochemical techniques (in which the cells have to be dead to be studied) as it allows the study of living cells allowing scientists to determine what happens to the cells’ biochemistry after a toxin is added. The multidisciplinary nature of our group has enabled us to make great strides in understanding the cause of POAG. Although much work remains, the continued generous funding from National Glaucoma Research will help us to find a cure for primary open angle glaucoma.