Current concepts and future directions in the pathogenesis and treatment of non-infectious intraocular inflammation

Abstract

The blockbuster drug paradigm is under increasing scrutiny across the biopharmaceutical industry. Intraocular inflammation poses particular challenges to this, given the heterogeneity of conditions in the uveitis spectrum, and the increasing acknowledgement of individual patient and disease variance in underlying immune responses. This need has triggered a drive towards personalised and stratified medicine, supported and enabled as a result of continued development of both experimental models and molecular biological techniques and improved clinical classification. As such we have the ability now to systematically appraise at a genomic, transcriptomic, and proteomic level individual immunophenotype, and the promise that in the eye this can be augmented by in vivo immune imaging to identify individual immunopathology. With such advances all running in parallel, we are entering an era of experimental medicine that will facilitate early diagnosis, generate biomarkers for accurate prognostication, and enable the development of individualised and targeted therapies, which can progress rapidly into clinical practice.

Autoimmune uveitis: clinical, pathogenetic, and therapeutic features

“…In addition, the experimental models of AU, in spite of their undisputable usefulness, do not reproduce exactly the complex relationships between the immune system and the eye [9]. Nevertheless, it has been hypothesized that a number of inflammatory processes may induce an aberrant T cell-mediated immune response that breaks down the blood-retinal barrier and acts against retinal antigens or cross-reactive antigens [52,53]. The retinal antigens involved are most probably components of melanocytes or tyrosinase or tyrosinaserelated proteins [54,55], such as retinal arrestin (S-antigen), inter-photoreceptor retinoid-binding protein, recoverin, melanin proteins and their products, and rhodopsin [56].…”

Juvenile idiopathic arthritis-associated uveitis

“…At the cellular level, there appears to be involvement of both T and B lymphocytes in generating an immune response against native intraocular antigens including S-arrestin (also known as retinal S-antigen), retinolbinding protein 3, and tyrosinase-related proteins [25]. Evidence for the involvement of both B and T lymphocytes comes from immunohistochemistry of eye biopsies from patients with JIA which show a predominance of CD4 + rather than CD8 + T lymphocytes as well as variable levels of CD20 + B lymphocytes.…”

Anti-Inflammatory Mechanisms of the Annexin A1 Protein and Its Mimetic Peptide Ac2-26 in Models of Ocular Inflammation In Vivo and In Vitro

“…However, some inflammatory processes can cause damage to ocular tissues, such as uveitis, an important cause of blindness worldwide (3). This ocular condition is prevalent in young adults and may be caused by injury or bacterial and parasitic infection or as a consequence of other systemic diseases, such as autoimmune disorders (4)(5)(6)(7).…”