title: Understanding autoimmunity in the eye: from animal models to novel therapies.
abstract: In recent years considerable headway has been made on understanding the mechanisms underlying inflammatory diseases of the eye. This includes the role of the innate vs. adaptive arms of the immune systems in disease, the concept that distinct immune pathways can drive end-organ pathology, and the role as well as limitations of immune privilege in controlling the innate and adaptive effector responses that lead to eye pathology and loss of vision. These insights have largely been derived from basic studies in established and in newly developed animal models of uveitis. The increased understanding of disease mechanisms has the potential to guide development of rational therapies for human uveitis. Many novel biologics currently in use or being evaluated have been developed, or validated, in animal models of autoimmune and inflammatory disease, including experimental uveitis. Paradoxically, and fueled in part by dwindling research budgets, a campaign has been gathering momentum against use of animal models in preclinical research, as being poorly representative of responses in humans. Given the extensive genetic similarity between humans and laboratory rodents as revealed by the Human, Mouse and Rat Genome Projects, and the finding that almost all known disease-associated genes have orthologs in mice and rats, perhaps the problem is our still-insufficient understanding of mechanisms and inadequate knowledge of species differences, resulting in poor choice of models, rather than in an inherent unsuitability of animal models to represent human disease.
authors.affiliation: Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Rachel R
authors.initials: RR
authors.lastname: Caspi
mesh_terms: D000818:Animals; D015551:Autoimmunity; D005123:Eye / Q000276:immunology*; D006801:Humans; D023421:Models, Animal; D014605:Uveitis / Q000209:etiology / Q000276:immunology / Q000628:therapy