OCULAR MECHANISMS OF INFLAMMATORY DISEASES OF THE EYE

不同免疫病理机制在眼部疾病中的作用

The roles of different immunopathologic mechanisms in diseases of the eye are incompletely understood. Distinct local and/or systemic cellular and humoral mechanisms may have significantly different roles, either alone or in concert with other mechanisms, in causing ocular inflammation and damage to vital ocular structures and in controlling infectious agents in the eye. An understanding of the separate and collective roles of the different immunopathologic mechanisms in ocular inflammatory disease would be of great value towards the ultimate goal of separating protective from damaging effects of immune responses in the eye. Such responses are the cause of a substantial proportion of blindness world-wide. The present studies will concentrate on the interactions of immunopathologic mechanisms mediated by homocytotropic (e.g., IgE) antibodies, eosinophils and mast cells in four models of ocular allergy: 1) Experimental vernal conjunctivitis produced in guinea pigs by topical application of fluoresceinylovalbumin or ascarid antigens; 2) Experimental ocular onchocerciasis produced in guinea pigs by the injection of Onchocerca microfilariae; 3) Spontaneous hypersensitivity to environmental antigens in the atopic dog; 4) Retinal pigment epitheliopathy and retinal degeneration associated with an eosinophil choroiditis in ascarid-infected eyes. The effects of immunological manipulations (e.g. variations in route, timing and dosage of antigens, concomitant sensitization with other antigens, selective anti-inflammatory drugs) on the development of lesions in the vernal conjunctivitis model will be defined in detail. Local antibody production will be studied in cultures of conjunctival lymphoid cells. The roles of specific mediators (e.g. eosinophil chemotactic factors, eosinophil and mast cell constituents) in the vernal model, and in the retinal pigment epitheliopathy of ascarid-infected eyes, will be studied in vivo by application of injection of mediators to or into the eye, and in vitro by employing cultures of conjunctival, corneal, and retinal pigmented epithelial cells. The ability of anti-inflammatory drugs and immunological manipulations to affect the acute corneal inflammation caused by diethylcarbazamine citrate treatment of experimental ocular onchocerciasis in guinea pigs will be defined in detail.