Normal pressure glaucoma (NPG), a common disease with devastating peripheral and central visual loss, is a progressive optic atrophy with no known pathophysiology or effective therapy. Prospective screening of NPG sera in our eye clinic has identified a dramatically increase incidence (19%) of abnormal monoclonal paraproteins of the IgG, IgM and IgA class by serum protein electrophoresis and immunofixation. There were no paraproteins in he general population over age 60 is 3%). These findings are highly suggestive of autoantibody related optic neuropathy in NPG. Taking advantage of the highly successful paradigm for elucidating the autoantibody-mediated mechanism of a variety of peripheral neuropathies associated with monoclonal gammopathies, patients with paraproteinemias and NPG and immunohistochemical techniques. Human brain, optic nerve tissue, retina and other likely sources of pertinent neuro-ocular antigens will be screened. Immunoblotting with fractionated preparations of ocular and neural tissues and patients sera can demonstrate the presence of reactive bands that may be isolated, sequenced, and identified. Immunohistochemical techniques using patients sera on sectioned human and rat eyes can provide recognition, anatomical localization and further characterization of the putative autoantigen(s). The IgG and IgM from paraprotein serum can be purified and will be used to examine their possible pathogenicity in an animal model. The identification of the autoantigen(s) will permit the development of more sensitive ELISA diagnostic testing to determine the presence of autoantibodies in patients with NPG who may have antibody titers which cannot be detected by serum immunofixation methods. This will permit some patients in whom the diagnosis is currently based solely upon clinical examination, to be identified by a serum marker. The identification of a subgroup of NPG patients with autoantibodies may provide not only insight into the pathophysiology of the disorder and a serum marker for the disease, but provide the basis for a new treatment rationale utilizing current and developing modalities of immunomodulation and immunosuppression.
| Romano, C; Barrett, D A; Li, Z et al. (1995) Anti-rhodopsin antibodies in sera from patients with normal-pressure glaucoma. Invest Ophthalmol Vis Sci 36:1968-75 |
