Nonenzymatic Collagen Cross-Linking and Glaucoma

Glaucoma is a major cause of permanent blindness in the elderly population. There are many types of glaucoma, the most common type being primary open angle glaucoma. Primary open angle glaucoma is characterized by abnormally elevated intraocular pressure, optic nerve damage, and visual loss which may progress to total blindness. The chances of developing primary open angle glaucoma increase with increasing age, a family history of glaucoma, African-American ethnicity, diabetes mellitus, myopia, and hypertension. The elevated intraocular pressure in primary open angle glaucoma is thought to be due to obstruction of the fluid drainage mechanism in the eye. The fluid normally drains through the trabecular meshwork in the eye. Microscopic examination of the trabecular meshwork from patients with glaucoma have shown aging changes of the tissue associated with deposits which may block the fluid drainage. The exact nature and cause of these deposits in the trabecular meshwork of eyes with glaucoma is unknown. It is thought that these deposits in the trabecular meshwork may be due to abnormal proteins. These abnormal proteins may accumulate over time as tissue ages from a process called oxidative damage. Ascorbate (vitamin C) which is in high concentrations in the fluids inside of the eye may either protect or contribute to the aging of tissues from oxidative damage. The actual process of abnormal protein formation may be due to changes in the shapes of the proteins from the binding of sugars or ascorbate to the proteins. This process has been demonstrated in the skin of elderly individuals and diabetic patients. Also these abnormal proteins have been found in cataracts which are common in older individuals. Present biochemical techniques are unable to study the structures of these- abnormal proteins, but a newer technique using a powerful magnet, call Nuclear Magnetic Resonance (NMR), will be able to study these protein structures in their natural environment. The effect of these abnormal proteins on fluid drainage can be studied by perfusion experiments. The precise location of these abnormal proteins in the trabecular meshwork can be determined by creating antibodies which can attach to and label these proteins. We believe that investigating the structures of these abnormal proteins, how they are formed, how they affect fluid drainage, and where they are localized in the eye will lead to better ways of preventing or curing primary open angle glaucoma.