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.

Figure 1

Schematic representation of a targeted approach to disarming macrophages. (1) The monoclonal antibody, DX109, utilises the inhibitory myeloid receptor CD200R to inhibit macrophage activity and redress homeostasis in the tissue, while enabling maintenance of anti-inflammatory IL-10 production. (2) Similarly, inhibiting macrophage activation (as shown by anti-complement therapy) will suppress EAU, principally by switching off pro-inflammatory, nitric oxide (NO), IL-6, IL-1, and TNF secretion. (3) Preventing the influx of T cells to the eye through inhibition of their efflux from lymph nodes with FTY720 (Fingolimod) also successfully induces disease remission in animal models of intraocular inflammation.