Immunomodulation of autoimmune responses with monoclonal antibodies and immunoadhesins: treatment of ocular inflammatory disease in the next millennium
- Department of Ophthalmology, University of Aberdeen
- Department of Rheumatology, University of Leeds
- Department of Ophthalmology, University of Aberdeen
- Department of Rheumatology, University of Leeds
- Dr Andrew D Dick, Department of Ophthalmology, University of Aberdeen Medical School, Foresterhill, Aberdeen AB25 2ZD.
Non-infective inflammatory disease is a significant cause of ocular and associated systemic morbidity and, in cases of posterior intraocular conditions, results in severe visual loss in over 30% of cases.1 2 Steroids have long been used for the treatment of conditions such as uveitis,3 4 although their therapeutic window is small.5 In addition to the successful use of cyclosporin A over the past two decades, newer immunomodulatory agents have also been introduced such as tacrolimus6 and mycophenolate mofetil.7 8Despite their efficacy, all of these treatments have major drawbacks—patients require long term therapy and systemic side effects are common. Additionally, a significant proportion of patients remain refractory to therapy. With improvement in our knowledge of the immunobiology of non-infectious ocular inflammatory disease, however,9 10 and in our ability to develop and produce recombinant proteins, it has become possible to specifically target cells and mediators of the immune system. Novel therapeutics arising from such work include specific monoclonal antibodies (mAbs) and receptor-Ig fusion proteins (immunoadhesins or IAs).11
Understanding the immunobiology of non-infectious ocular inflammatory disease identifies specific targets for therapy
Non-infectious posterior intraocular inflammation (PSII), which includes uveitic disorders, and ocular surface inflammatory disorders, including scleritis and peripheral ulcerative keratitis (PUK), are arguably the commonest cause of immune mediated visual loss. Fifty per cent of these “autoimmune” disorders are limited to the eye (organ specific), whereas the remainder form part of more generalised diseases, including connective tissue and multisystem granulomatous disorders. Understanding basic immunopathological mechanisms from patients is hindered by the rarity of some diseases, genetic and clinical heterogeneity of patients, and limited access to clinical material from the site of disease. Consequently, most significant advances have arisen from experimental models of autoimmune disease, particularly with reference to the eye.12 Models of both posterior and anterior uveitis demonstrate a pivotal role for antigen specific CD4+ (T …
