IL-1 receptor antagonist in the treatment of dry eye disease

Abstract

Dry eye disease is a multifactorial, complex and chronic disease that entails an important inflammatory component. The prevalence of this condition continues to increase, with the potential to significantly reduce patients’ quality of life. Treatment options are limited, and thus new treatment options are continuously being investigated in the laboratory and in the clinic. IL-1 receptor antagonist is a targeted biologic that blocks the binding of IL-1α and IL-1β to their signaling receptor IL-1R1, thereby nullifying their inflammatory function. Treatment with topical IL-1 receptor antagonist has been shown to reduce inflammation in experimental dry eye in mice. Recently, a prospective, randomized, double-masked, vehicle-controlled clinical trial confirmed the previous preclinical results, and showed that topical application of IL-1 receptor antagonist significantly reduces corneal epitheliopathy and symptoms of discomfort in patients with dry eye disease.

Keywords::

• corneal epitheliopathy
• dry eye disease
• dry eye symptoms
• inflammation
• interleukin-1
• interleukin-1 receptor antagonist
• ocular surface

Financial & competing interests disclosure

R Dana has received funding from the NIH (grant number EY019098) and is listed as co-inventor in a patent application pertaining to use of IL-1 blockers for ophthalmic use, licensed by Schepens Eye Research Institute and Massachusetts Eye and Ear Infirmary to Eleven Biotherapeutics Inc. In addition, R Dana holds equity in Eleven Biotherapeutics Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Dry eye disease (DED) is a multifactorial condition that entails a sustained inflammatory component.

• IL-1 plays a major role in orchestrating the inflammatory response in DED.

• IL-1 receptor antagonist (IL-1Ra) inhibits the proinflammatory action of IL-1 by blocking its binding to the IL-1 cell receptor 1 (IL-1R1).

• Treatment with IL-1Ra has been shown to be effective in reducing the signs and symptoms of inflammatory ocular diseases that involve increased activity of IL-1.

• Topical application of IL-1Ra significantly reduces epitheliopathy, influx of inflammatory cells and lymphatic vessels in the corneas of mice with experimental DED.

• Topical treatment with IL-1Ra significantly reduces corneal epitheliopathy and symptoms in patients with DED compared with a lubricant vehicle.

• New chimeric molecules that are more stable and optimized for topical treatments, and show higher affinity to the IL-1 receptor than IL-1Ra, are being designed to specifically block the effects of IL-1 on the ocular surface.