Freeze Fracture Studies of Human Trabecular Meshwork

In order for the eye to maintain its shape and serve its optical functions, the fluid and gel-filled sphere of the eye is slightly pressurized. Under normal conditions new fluid is made continuously and drained continuously through a specialized filtering tissue known as the trabecular meshwork. After passing through the trabecular meshwork, fluid enters a special blood vessel termed Schlemm’s canal which drains into venous blood leaving the eye. In order to maintain a pressure and yet allow for continuous exchange of fluid, a resistance to fluid flow must exist somewhere in the fluid flow pathway. Many believe that this resistance lies in or near Schlemm’s canal. If the resistance to fluid flow out of the eye is too high, the pressure in the eye can reach levels that damage the nerve cells in the back of the eye that absorb light. The result is progressive blindness from one of a group of diseases collectively called glaucoma. In the most common form, it is believed that increased resistance to fluid outflow is a significant contributor to the development of the disease. The goal of our studies is to examine certain anatomical structures that we believe may play a role in creating outflow resistance. These structures are called intercellular junctions. Specifically, we wish to examine the structure of the junctions that hold together the cells lining the wall of Schlemm’s canal. We know that fluid resistance drops if these junctions are disrupted but their actual structure in the normal human eye has never been examined. Similarly, we do not know if these junctions change in any predictable way when pressure or flow conditions in the eye are changed as would occur in glaucoma. Using a specialized anatomical technique called freeze-fracture electron microscopy is the only method available to visualize the actual structure of the extremely small junctions that join individual cells to one another. In the proposed studies we will examine the junctions that exist between cells lining Schlemm’s canal of the normal human eye under various pressures to determine if and how their structure changes. Identical studies will be completed on glaucomatous eyes to determine what role these junctions might play in increasing resistance to the flow of fluid from the eye. Our hypothesis is that changes induced in the structure of junctions either with age or by changes in pressure or flow result in additional resistance to fluid outflow that may contribute to the development of glaucoma.