Molecular mechanism of intractable ocular diseases

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Intractable ocular diseases often recur, and their visual prognosis is usually poor. We have studied molecular immunology, molecular genetics, and molecular epidemiology of intractable endogenous uveitis, allergic conjunctival diseases, and adenovirus conjunctivitis.In Behcet's disease, the same genetic association with Japanese patients was found in Greek patients, such as HLA-BィイD1*ィエD15101, and MICA-A6. Glucose intolerance was found in patients with Vogt-Koyanagi-Harada disease. Acute inflammatory cytokines were thought to be the main cause of the glucose intolerance, similar to other autoimmune diseases. Soluble intercellular adhesion molecules were important for the determination of disease activity.In allergic conjunctival diseases, soluble ICAM-1, soluble IL-2, and soluble VCAM-1 in the sera were found to play important roles in the pathogenesis. Among them, soluble VCAM-1 was specifically associated with vernal keratoconjunctivitis, and not with the atopic dermatitis. Histamine release test using small amount of whole blood was also revealed to be a useful test for the determination of responsible antigen. In Atopic dermatitis, the patients with ocular manifestation have significantly higher IgE titer against rice and wheat than the patients without ocular manifestation.In adenovirus conjunctivitis, new genointypes of adenovirus 3 were found. We have successfully applied the PCR-sequence method for the detection of adenovirus serotypes. In the study of adertovirus conjunctivitis during the last 10 years, the dominant serotype of various adenoviruses has been changing every 3-5 years. We have also found certain number of herpes virus conjunctivitis and chalamydial conjunctivitis cases.These results indicate that it is important and rewarding to study the molecular mechanisms of various intractable ocular diseases.