Experimental Models in Autoimmune Uveitis

Abstract

Autoimmune uveitis, a complex ocular inflammatory disorder, remains a significant challenge in ophthalmology and immunology research. This chapter delves into the intricate world of experimental models designed to mimic autoimmune uveitis in humans. We provide a comprehensive examination of these models, focusing on their utility, strengths, and limitations. First, we explore well-established experimental models, such as the classic rodent models induced by immunization with uveitogenic antigens, including interphotoreceptor retinoid-binding protein (IRBP) and retinal soluble antigen (S-Ag). These models have played a pivotal role in deciphering the immunopathogenic mechanisms underlying autoimmune uveitis. We discuss the methodologies employed to induce uveitis in these models and the histological and clinical correlates, shedding light on the similarities and differences with human disease. Furthermore, this chapter presents emerging experimental models, including genetically modified animals with targeted immune system alterations, such as knockout mice and transgenic models. These genetically engineered models allow researchers to dissect specific immune pathways involved in uveitis pathogenesis, offering a deeper understanding of the disease's immunological basis. In addition to animal models, we explore in vitro and ex vivo systems, such as organotypic retinal explants and co-culture systems, which enable the investigation of cell-cell interactions and the role of various immune cell populations within the ocular microenvironment. Throughout this chapter, we have discussed the critical insights gained from these models, including the identification of key immune cells, cytokines, and signaling pathways contributing to uveitis development. We also addressed the challenges and translational considerations when applying findings from experimental models to human autoimmune uveitis. Ultimately, this comprehensive analysis of experimental models for autoimmune uveitis research aims to provide researchers and clinicians with a valuable resource to enhance our understanding of the disease, facilitate the development of targeted therapies, and ultimately improve patient outcomes in the field of ocular immunology.