Antigen Identification in Occult Chorioretinopathies

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DESCRIPTION (provided by applicant): Acute zonal occult outer retinopathy, multiple evanescent white dot syndrome, acute macular neuroretinopathy, acute idiopathic blind spot enlargement syndrome, multifocal choroiditis, punctuate inner choroidopathy, and diffuse subretinal fibrosis syndrome are a group of chorioretinal inflammatory disorders of unknown etiology. These disorders possess common clinical features, and affected individuals may evolve from one condition to another during their clinical course. Vision loss may vary from mild to severe. To date, however, there are no absolute criteria to define disease subtypes, no available markers to diagnose disease or gauge prognosis, and no effective therapies. As a result, debate remains as to whether these disorders represent a related spectrum of inflammatory chorioretinopathies. Pathologic specimens have revealed a B-cell predominant inflammatory infiltrate with antibody deposition providing a rationale for our hypothesis that antibodies play a role in the pathogenesis of these disorders and are directed against retinal or choroidal antigens that trigger or propagate disease. To identify an antigen specific to occult chorioretinopathies (OC) we will: (1) identify clones in a human uveal cDNA expression Library and a random peptide library whose products react with serum from OC patients; (2) determine the disease-specificity of candidate QC-specific antigens and peptides by screening sera from patients with QC and control ocular uveitides; and (3) characterize, using molecular biologic techniques, OC-specific clones and study their pattern of expression in the retina and choroid. Identification of OC-specific markers will help classify these occult inflammatory disorders as a specific nosologic entity, generate biologic markers to diagnose preclinical and clinical disease, and develop therapeutic strategies to prevent loss of vision in affected individuals.