Topical biological agents targeting cytokines for the treatment of dry eye disease

Abstract

Because inflammation plays a key role in the pathogenesis of dry eye disease and Sjögren’s syndrome, topical anti-inflammatory agents such as corticosteroids and cyclosporine A have been used to treat inflammation of the ocular surface and lacrimal gland. Systemic biological agents that target specific immune molecules or cells such as tumor necrosis factor (TNF)-α, interferone-α, interleukin (IL)-1, IL-6, or B cells have been used in an attempt to treat Sjögren’s syndrome. However, the efficacy of systemic biological agents, other than B-cell targeting agents, has not yet been confirmed in Sjögren’s syndrome. Several studies have recently evaluated the efficacy of topical administration of biological agents targeting cytokines in the treatment of dry eye disease. Topical blockade of IL-1 by using IL-1 receptor antagonist could ameliorate clinical signs and inflammation of experimental dry eye. Using a mouse model of desiccating stress-induced dry eye, we have demonstrated that topical application of a TNF-α blocking agent, infliximab, could improve tear production and ocular surface irregularity, decrease inflammatory cytokines and Th-1 CD4+ cells on the ocular surface, and increase goblet cell density in the conjunctiva. Although controversy still remains, the use of topical biological agents targeting inflammatory cytokines may be a promising therapy for human dry eye disease.

Keywords: Dry eye disease; Sjögren’s syndrome; Biological agent; Tumor necrosis factor-α; Interleukin-1; B cell; Cytokine

Core tip: Although the debate remains about the efficacy of systemic biological agents on Sjögren’s syndrome, topical biological agents targeting inflammatory cytokines can be applicable for the treatment of dry eye disease.