Three Dimensional Analysis of Trabecular Meshwork

Glaucoma remains one of the leading causes of blindness in this country and throughout the world. Development of new, more effective treatment, and the future promise of an ultimate cure depend upon understanding the basic cause or abnormality of the eye producing the high pressure characteristic of the disease. At present, the exact cause is not known. The normal eye is filled with a clear fluid, called the aqueous humor, which is made and drained out of the eye every day. In glaucoma, the drainage channels (trabecular meshwork) become plugged, and the fluid cannot drain from the eye. This causes a buildup of fluid, with a resulting increase in pressure within the eye and damage to the optic nerve. Although the drainage channels have been studied for over 80 years, the exact mechanism as to how they become plugged remains unknown. Microscopic examination of the trabecular meshwork does not find specific abnormalities in glaucoma, but rather the excess accumulation of material normally present. The trabecular meshwork is a series of small channels and canals which interweave and wind through the tissue, much like the various holes in Swiss cheese. Conventional microscopic examination is usually done in one plane or orientation. The trabecular meshwork has a different appearance when looked at from different directions, however. Combining these different views or orientations into recognizable pictures or structures (three dimensional reconstruction) is difficult. It may be the only way to discover the problem in glaucoma, however, as we are unable to tell if a channel has become narrowed or closed when looking at only a thin slice of it (conventional two dimensional microscopy).

Hypothesis

Three dimensional analysis of the trabecular meshwork may find narrowing or closure of channels in the trabecular meshwork which cannot be found using conventional two dimensional microscopy. Three dimensional analysis of the meshwork will give a greater understanding of the tissue in looking for the cause of glaucoma.

Specific Aim

We propose to apply a three dimensional reconstruction method, developed at our institution, to examine the trabecular meshwork.

Goals

Once a reliable method for three dimensional analysis and viewing of the trabecular meshwork has been developed, we will examine eyes with glaucoma. We will look for closure of drainage channels and pathways, and also look for the presence of excess material in these pathways. Once a specific material can be found which is narrowing the drainage channels, the cause for its excess production can be sought by using the techniques of molecular biology to examine factors regulating its DNA. A great advantage in this project is our ability to work directly with the initial developers of the computer program. This will enable us to refine program, with rewriting portions of it as needed, to obtain clear and useful images of the trabecular meshwork.