Molecular And Immunopathology Of Ocular Diseases

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The identity and topographic location of ocular inflammatory, degenerative, and tumor cells and their products in patient specimens are analyzed by routine pathology, immunohistochemistry, in situ hybridization, microdissection and various molecular techniques including PCR, RT-PCR, and RFLP assay. The application of cutting-edge technology allows us to provide accurate pathological assessments of the disease, guides us in selecting an appropriate therapy for the patient, and helps us to better understand the disease mechanisms. In FY2005, we continued and accomplished the following in our research: 1. Detection of Genes and Proteins in Ocular Lymphoma Cells: We continued to detect IgH gene rearrangements and vitreal IL-10 elevations as useful adjuncts for primary intraocular B-cell lymphoma (PIOL) diagnosis. Seven more new cases were diagnosed with PIOL. 2. New Pathology and Pathogenesis of Ocular Inflammation and Other Diseases: We reported decreasing uveitic activities during pregnancy. We studied the pathology of 33 AIDS autopsied eyes with ganciclovir implants and found that they were well tolerated within the eyes. Using microdissection and molecular analysis, we were the first group to detect Helicobacter pylori (H. pylori) DNA in the conjunctival mucosa-associated lymphoid tissue (MALT) lymphoma. We also identified loss of heterozygosity in the von Hippel-Lindau (VHL) gene in vacuolated "stromal" cells of optic nerve hemangioblastoma and demonstrated high expression of hypoxia-inducible factor (HIF) and ubiquitin in the VHL cells. 3. Experimental Models for Various Inflammatory and Other Ocular Diseases: We developed a new murine model for primary intraocular lymphoma. We reported a novel mouse model for ocular surface disease and resultant blindness with X-linked anhidrotic ectodermal dysplasia disruption. We continued to investigate the role of inflammatory mediators and cytokines in the endotoxin-induced uveitis (EIU) model, a model for human anterior uveitis. We reported enhanced EIU in cyclooxygenase-2 (COX2) deficient mice, in which interferon-gamma could moderatedly reverse this exacerbation and protect against EIU. In collaboration with Drs. Caspi, Gery, and Nussenblatt, several new modes and mechanisms of ocular inflammation have been discovered and published.