IMMUNOPATHOLOGY IN EYES WITH EXPERIMENTAL AND CLINICAL OCULAR DISEASES

免疫活性细胞的身份和地理定位

The identity and topographic localization of immunocompetent cells and the alteration of cellular markers on ocular resident cells in animals with various experimental uveitis were analyzed by immunohistochemistry and in situ hybridization. Previously, we have demonstrated that T lymphocytes, in particular the CD4 cells, were the predominant infiltrating cells in experimental autoimmune uveoretinitis (EAU) and experimental melanin-protein induced uveitis (EMIU), yet both macrophages and polymorphonuclear neutrophils were the predominant infiltrating cells in endotoxin-induced uveitis (EIU) and all types of leukocytes were present in murine experimental blepharitis. Cytokines (e.g., lymphokines) and inflammatory mediators (e.g., nitric oxide) play an important role in the immunopathogenesis of uveitis. Expressions of major histocompatibility class (MHC) II antigens and adhesion molecules are observed on ocular resident cells during the inflammatory process. We have studied transforming growth factor-beta (TGF-beta1), one of the cytokines that modulates inflammation in rodent EMIU, murine EIU, and TGF-beta1 transgenic mice. TGF-beta1 inhibits the recurrence of EMIU by shifting Th1 to Th2 cytokine profile. Systemic TGF-beta1 suppresses EIU and serum IL-6 levels. Progressive cataract and transient retinal edema develop in TGF-beta1 transgenic mice. However, no significant differences in the induction of EIU were found between the transgenic mice and the wild-type controls. We have concluded that TGF-beta1 regulates inflammation through the complex cytokine network and may be useful for the treatment of human uveitis. Other cytokines and inflammatory mediators may also be beneficial for therapy. Nitric oxide protects against ocular Toxoplasma gondii and limits the immune response. IL-12 inhibits EIU. Specimens from human ocular tissues with various diseases, including uveitis, retinal and corneal diseases, tumors, and metabolic genetic disorders, are studied by using routine histological, immunohistochemical, and in situ hybridization techniques. In uveitis, immunocompetent cells and cytokines, in addition to the stimulators (e.g., infectious organisms), are valuable adjuncts for making a clinical diagnosis and understanding the pathogenesis of the diseases. Elevation of IL-10 in the vitreous helps to diagnose intraocular large B-cell lymphoma, which frequently masquerades as idiopathic uveitis. We have reported that metastatic choroidal bacterial abscess occurs in AIDS, and the thickened cell wall structure of Propionibacterium acnes may relate to the resistance of bacterial killing and degradation by the host neutrophils and macrophages. Elucidating the immunopathological role of the relationship between the infiltrating cells and ocular resident cells will help us gain a better understanding and management of various ocular diseases in patients.