Abstract
The profound impact that vision loss has on human activities and quality of life necessitates understanding the etiology of potentially blinding diseases and their clinical management. The unique anatomic features of the eye and its sequestration from peripheral immune system also provides a framework for studying other diseases in immune privileged sites and validating basic immunological principles. Thus, early studies of intraocular inflammatory diseases (uveitis) were at the forefront of research on organ transplantation. These studies laid the groundwork for foundational discoveries on how immune system distinguishes self from non-self and established current concepts of acquired immune tolerance and autoimmunity. Our charge in this review is to examine how advances in molecular cell biology and immunology over the past 3 decades have contributed to the understanding of mechanisms that underlie immunopathogenesis of uveitis. Particular emphasis is on how advances in biotechnology have been leveraged in developing biologics and cell-based immunotherapies for uveitis and other neuroinflammatory diseases.
Highlights
The vertebrate immune system is comprised of the adaptive and innate immune systems and the two limbs have unique as well as overlapping functions that are seamlessly integrated [1]
Posterior uveitis poses the greatest risk of blindness and the best characterized model of posterior uveitis is experimental autoimmune uveitis (EAU) [28,29,30]
Analysis of EAU in these mice has revealed that gut commensals might be a source of signals that prime autoreactive retina-specific T cells to trigger uveitis [36]
Summary
The vertebrate immune system is comprised of the adaptive and innate immune systems and the two limbs have unique as well as overlapping functions that are seamlessly integrated [1]. During antigen priming in secondary lymphoid or peripheral tissues, innate immune cells such as dendritic cells (DC) secrete cytokines that instruct the naïve lymphocyte to differentiate and generate effector lymphocyte subsets that orchestrate humoral or cell-mediated immunity to pathogens [2]. The immense capacity of lymphocyte response to diverse antigens derives from diversity of their cell surface antigen receptors and a critical function of the immune system is to establish tolerance against self-antigens while allowing selective immunity to pathogens [3, 4]. Exuberant effector immune responses that cause pathogenic autoimmunity are restrained or prevented by specialized regulatory cells that secrete immune-suppressive cytokines [5]. Defects in central and/or peripheral tolerance mechanisms can result in autoimmune diseases such as uveitis, the focus of this review. The embryonic vertebrate retina and optic nerve derive from the diencephalon of the developing brain and are considered part of the CNS. The retina is an immune privileged tissue
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