A look at autoimmunity and inflammation in the eye

Abstract

Autoimmune and inflammatory uveitis are a group of potentially blinding intraocular inflammatory diseases that arise without a known infectious trigger and are often associated with immunological responses to unique retinal proteins. In the United States, about 10% of the cases of severe visual handicap are attributed to this group of disorders. As I discuss here, experimental models of ocular autoimmunity targeting retinal proteins have brought about a better understanding of the basic immunological mechanisms involved in the pathogenesis of uveitis and are serving as templates for the development of novel therapies.

Doyne lecture 2016: intraocular health and the many faces of inflammation

“…24,[32][33][34] The clinical phenotype of non-infectious intraocular inflammation is replicated in experimental animal models that are driven by immune responses to self-antigen. 35 The animal models, such as experimental autoimmune uveoretinitis (EAU), support a role for autoimmunity with clinical-pathological features bearing remarkable similarity to man. 7,8,36,37 The currently held notion is that of a CD4 + T helper cell-driven process and supported in man by the association of sympathetic ophthalmia and Vogt-Koyanagi-Harada disease with specific HLA class II alleles as well as the identification of ocular antigen-responsive T cells in both the peripheral blood and eyes of patients.…”

Lipopolysaccharide‐primed heterotolerant dendritic cells suppress experimental autoimmune uveoretinitis by multiple mechanisms

“…In most cases the aetiology of uveitis is unknown, although bacterial and viral infections, as well as systemic diseases, are recognized causes and associations. Autoimmunity to retinal or other ocular antigens is considered to be mechanistic in non‐infectious uveitis 3. Treatment of non‐infectious uveitis centres around non‐specific therapy using immunosuppressive agents, or biologics such as anti‐tumour necrosis factor‐ α (TNF‐ α ) antibodies 4, 5.…”

Bowman lecture on the role of inflammation in degenerative disease of the eye

“…14,15 However, the variety of pathological lesions is relatively restricted (granulomas, cellular infiltration, oedema, and vasculitis) and remarkably experimental uveitis induced by a single antigen can reproduce much of the spectrum of disease similar to that found in human IOI, suggesting a common variably severe pathogenic mechanism. 16 EAU as a model has been described in great detail in several excellent reviews previously 5,17 and only brief summary details of the acute disease are given here.…”

“…However, the situation remains unstable for some time and recurrence can occur. This less aggressive model of EAU, with its potential for recurrence, has closer similarity to many human forms of posteriors uveitis 5 and has therefore gained in popularity for preclinical studies (reviewed in Forrester et al 21 ).…”

“…SO can be regarded as the first autoimmune disease, known for centuries as a consequence of war injures and first reported in the English language in a clinico-pathological description by Mackenzie 2 even before Immunology as a discipline was born. It was not for another century or more, however, with the use of Bowman's 'lower' animal models, that the nature of ocular autoantigen(s) was discovered 3,4 and the pathogenic mechanisms of intraocular inflammation (IOI), or more commonly uveitis, began to be unravelled (reviewed in Caspi 5 ).…”