Molecular And Immunopathology Of Experimental And Clinic

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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 such as 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 FY2006, we continued and accomplished the following in our research: 1. Detection of Genes and Proteins in Ocular Lymphoma Cells: We reported bcl-2 t(14;18) translocation in 56% of 72 cases with primary intraocular lymphoma (PIOL). Although there was no significant association between bcl-2 t(14;18) translocations and survival or relapse. Patients with translocation were significantly younger. We also reported a relationship between PIOL and testicular lymphoma. We detected infectious genes (H. pylori or C. peumoniae) in conjunctival and orbital MALT lymphoma. 2. Molecular pathology of age-related macular degeneration (AMD): We detected higher rates of single nucleotide polymorphisms and lower expression of CX3CR1 and ERCC6 in the AMD maculae compared to the normal eyes, which confirmed the association studies of these two genes and AMD. 3. New Pathology and Pathogenesis of Ocular Diseases: We discovered stem cell components in ocular hemangioblastomas associated with von Hippel-Lindau disease. We reported ocular pathology of Hermansky-Pudlak syndrome type 1 in an adult whose ocular melanocytes were sparse and contained mainly stage III and rarely stage IV melanosomes. We observed long term survaval of donor epithelial cells after limbal stem cell transplantation, which implied the need of immunosuppresive therapy. We discussed mycobacterium related ocular infalmmatory diseases, and ocular findings in chronic granulomatous disease. 4. Experimental Models for Various Ocular Diseases: We demonstrated exacerbation of retinal degeneration and choroidal neovascularization induced by subretinal injection of matrigel in CCL2/MCP-1 deficient mice, which supported the important role of inflammation played in AMD. In collaboration with Drs. Caspi, Gery, and Nussenblatt, several new modes and mechanisms of ocular inflammation have been discovered and published. In collaboration with Dr. Chew, we found elevated serum inflammatory markers such as ICAM-1, RANTES and CCL2 in patients with diabetic retinopathy.