Gene Therapy for Noninfectious Uveitis

Noninfectious intraocular inflammatory disease remains a significant cause of visual loss, even with current systemic immunosuppression. Alternative novel treatments are thus required, particularly for severe forms of posterior uveitis. Encouraging results from several phase I/II clinical trials of gene therapy for monogenic retinal disorders have paved the way for the development of this approach for other ocular conditions. Gene therapy for uveitis offers the possibility of potent, self-regulating, long-term disease control following a single treatment and without systemic side effects. To date, gene therapy approaches using interleukin-10, interleukin-1 receptor antagonist, interferon-alpha, soluble TNF-alpha receptors, and alpha-MSH gene transfer have been used successfully to attenuate experimental animal models of uveitis. This review evaluates these preclinical studies, considers the route to clinical application, and explores future targets and approaches.