Experimental Ocular Inflammation

National Eye Institute

Investigators

Linked publications & trials

Abstract

More than 1 million Americans are affected by uveitis (ocular inflammation) and approximately 45,000 new cases are diagnosed each year. Additionally, in the USA, approximately 10% of all blindness cases are due to uveitis complications including corneal scarring, cataract, glaucoma, macular edema, etc? Our group is interested in analyzing the mechanisms involved in various types of ocular inflammation. Therefore, we developed animal models mimicking human ocular inflammatory diseases. Among these, endotoxin-induced uveitis (EIU) is a model for acute anterior uveitis (AAU), experimental melanin protein-induced uveitis (EMIU) is a model for autoimmune uveitis, experimental toxoplasmosis is a model for infectious acquired toxoplasmic retinochoroiditis and allergic conjunctivitis is a model for seasonal allergic conjunctivitis (SAC), a type I hypersensitivity disorder. We analyzed the role of Fas-mediated apoptosis (programmed cell death) in our murine ocular toxoplasmosis model in which mice are injected intraperitoneally with bradyzoites. This model is close to the human acquired disease where Toxoplasma gondii (T. gondii) infection usually starts through eating. In our model, lpr and gld mice (deficient in the 2 components of Fas mediated apoptosis) do not show significant differences in apoptosis or parasitic disease compared to wild-type controls. Additional data indicate that lpr and gld mice express IFN-gammma mRNA significantly earlier than wild-type controls. Additionally, ocular NO production is significantly increased. Our data indicate that in the absence of Fas-mediated apoptosis, mice can still control T. gondii infection by increasing IFN-gamma and NO production. In FY2001, we further analyzed the therapeutic role of DNA containing unmethylated CpG oligodinucleotide motifs (CpG-ODN) in allergic conjunctivitis. Such DNA are apparently mediating the induction of Interferons and IL-12. We showed that mucosal administration of CpG-ODN inhibits allergic conjunctivitis in a ragweed murine model. Our data indicate that CpG-ODN inhibits both the immediate hypersensitivity response and the late phase cellular infiltration. Additionally, a ragweed specific Th1 response is initiated and the production of anti-ragweed IgE is suppressed. We demonstrated that CpG-ODN have a protective effect when applied topically after the disease has already been established. This has important implications in the treatment of patients with allergic conjunctivitis as it can prevent the recurring of the allergic disease.