Nancy McNamara, OD, PhD

Associate Professor
University of California, Berkeley
Berkeley, CA

Jes Klarlund, PhD

Pittsburgh, PA
A New Generation of Eye Drops to Treat the Ocular Manifestations of Sjögren’s Syndrome

The Lay Abstract is for publicity purposes and should use simple language summarizing the proposed research and its significance.

Sjögren’s Syndrome is usually associated with severe dry eye that is debilitating and highly recalcitrant to current therapies. A number of proteins are known to suppress the inflammatory response that causes dry eye, but they have little or no effect when applied to the eye because they are washed out quickly by blinking. We are proposing a method to make these proteins “sticky” so they remain at the surface of the eye after topical application and therefore have time to act. We will create a sticky version of a therapeutic protein, which has proven effective for treating inflammatory diseases like rheumatoid arthritis and shows promise as an effective therapy for dry eye. The technology is very versatile and will allow development of eye drops to address other eye problems in Sjögren’s Syndrome such as corneal haze, pain, and insufficient secretion of tears.

The Scientific Abstract is written for SSF reviewers and a professional audience.

Dry eye is an onerous manifestation of Sjögren’s Syndrome (SS), and there is a great unmet need to develop effective therapies. The short residence time on the ocular surface significantly limits or eliminates the efficacy of the majority of potential topical ophthalmic therapeutics. We are developing a novel drug delivery system by fusing an anchor domain that binds to abundant extracellular molecules to therapeutic proteins so they are retained at the corneal surface. Preliminary data demonstrate that a protein containing an anchor domain remains attached and active at the ocular surface for at least 16 hours. We propose
to deliver an anti-inflammatory protein, anakinra, to the ocular surface of a mouse model for dry eye in SS. The system is very versatile and can be used to deliver other bioactive proteins for instance to enhance innervation, to counter corneal opacification, and to study pathological processes in SS.