Autoimmunity and Normal Pressure Glaucoma

The progressive optic nerve disease that is accompanied by normal intraocular pressure, clinical signs of optic nerve changes and loss of side vision is commonly termed “normal pressure glaucoma” and its etiology is presently unknown. However, there is some evidence that optic nerve damage in some of the patients with normal pressure glaucoma may involve an immune mechanism associated self proteins, and we have been examining this possibility. We have recently found an increased immunological response to a protein called of heat shock protein 60, or hsp60, in the sera of patients with normal pressure glaucoma. Heat shock proteins are abundant proteins in nature and play an important role in cell survival under many environmental stresses as well as under normal conditions. They are believed to help form and maintain the proper structure of other proteins into the cells and their importance in the development and survival of neuron cells are well known. It has recently been shown that they may have protective effects on retinal ganglion cells (nerve cells of eye important for vision) that have been stressed. However, the detailed mechanisms involved have not been elucidated. They are also important proteins of numerous pathogenic bacteria and there are high degree of biologic similarities between bacterial and human heat shock proteins. It is well known that immune responses to these proteins may be initiated by a bacterial infection and then the reaction may be turn to self proteins and cause disease. Such a mechanism has been suggested in numerous diseases, including insulin dependent juvenile diabetes, multiple sclerosis and rheumatologic diseases.

Since we have found antibodies against heat shock proteins in the blood of many patients with NPG, and since heat shock proteins contribute to retinal cell health and resistance to stress, we hypothesize that antibodies against these protein may therefore render retinal cells more susceptible to stress such as decreased blood flow. Serum antibodies to heat shock protein in patients with normal pressure glaucoma may therefore predispose towards retinal cell death. In the proposed experiments we will determine the the presence of heat shock proteins, or antibodies to heat shock proteins, affects the vulnerability of the retina to stressful stimuli. We will observe the release of lactate dehydrogenase from cells and subsequent extracellular appearance as a marker of the death of neuron cells. In addition, we will perform a specific test, quantitative western blotting, to assess the level of retinal heat shock proteins in response to the stress conditions such as increased heat and decreased blood flow. We believe that understanding the role of heat shock proteins on retinal injury may serve to help rescue injured neurons from death in glaucoma patients.