Biological Therapies that Target Inflammatory Cytokines to Treat Uveitis

Abstract

Uveitis is a leading cause of blindness that presents a considerable challenge given that our understanding of the mechanisms of disease is still evolving. Both innate and adaptive immunity play a role in disease and mediators of these responses can serve as therapeutic targets. TNF-α and IL-1β inflammatory cytokines are central mediators of immunity and are involved in the dysregulated inflammatory response during uveitis. Because toxicity limits the use of steroids and other steroid-sparing agents, biologics that target a specific cell type or pathway are being explored for the treatment of autoimmune uveitis. This chapter begins with a broad overview of the aberrant immune response resulting in uveitis, and highlights key mediators such as TNF-α, IL-1β, IL-6, and IL-17 and their potential use as therapeutic targets. Most biological agents discussed in this review have not been FDAapproved for uveitis. However, favorable outcomes in early trials and FDA approval of these drugs for the treatment of other autoimmune diseases associated with uveitis support the potential for these biological agents in the management of uveitis. This review aims to provide an updated report on the efficacy of biologics that target TNF-α, IL-1β, IL-6, and IL-17 for the treatment of autoimmune uveitis.

Low-dose melittin is safe for intravitreal administration and ameliorates inflammation in an experimental model of uveitis

“…Increased production and secretion of these mediators have also been observed in ocular fluids and serum from patients with uveitis when compared to healthy controls ( Carreño et al., 2016 ; Fukunaga et al., 2020 ). Furthermore, TNF-α, IL-6, and IL-1β are central mediators of ocular inflammation, which lead to activation of both innate and adaptative immunity ( Reddy et al., 2018 ). In addition, increased production of NO during the inflammatory process within the eye can result in cell damage, especially photoreceptors, which was detected in the histopathological analysis of the vehicle-treated group ( Saraswathy and Rao, 2008 ).…”