Research News

The National Eye Institute, part of the National Institutes of Health, has awarded Feng Lin, PhD, a four-year, $1.6 million grant to investigate the biological mechanisms underlying autoimmune uveitis (AU), a common cause of blindness. The long-term goal of the preclinical study is to gain insights into the causes of AU that may reveal novel targets and help researchers develop therapies to treat the disease in patients.

Autoimmune uveitis is an autoimmune disease of the eye characterized by inflammation in the eye and retinal tissue destruction. The causes of AU currently remain unknown and there are no available cures.

Dr. Lin’s laboratory focuses on the complement system’s role in the pathogenesis of many different diseases. The complement system enhances the ability of antibodies and other components to attack and destroy foreign invaders. While these systems are helpful in fighting infections, for autoimmune diseases, like AU, where the body mistakenly recognizes itself as a threat, overactive immune responses are the focus of many therapeutics.

The role of complement and T cells

Complement, a key component of innate immunity, can also interact with elements of the adaptive immune system, including T cells, and plays critical roles in regulating the adaptive immune system.

“Our previous data suggested that the complement system is integrally involved in regulating the infiltration and re-stimulation of already primed T cells in the retina,” said Dr. Lin, staff in the Department of Inflammation & Immunity. “This new grant will enable us to expand our previous work and will support preclinical research to identify the specific mechanisms of complement-T cell interactions in the retina in the context of AU.”

Two decades of studying complement

Two decades of previous research by the team has shown that complement plays an important role in models of AU. Preclinical AU models genetically engineered to not express certain complement components or receptors had significantly decreased retinal inflammation and reduced autoreactive T cell responses. The studies also suggested that in addition to its critical role in regulating T cell activation in the periphery, complement also facilitates activated T cells to migrate through the blood-retina barrier and helps these pathogenic T cells get re-stimulated in the retina to induced uveitis. 

In this new study, Dr. Lin and his team will also test the efficacy of several complement inhibitors in treating AU models.

“We hope to determine the role of complement in regulating the migration and re-stimulation of primed autoreactive T cells in the target tissues and elucidate the underlying mechanisms,” said Dr. Lin. “Our long-term goal is to lay the foundation for complement inhibitors as a new therapeutics for treating this blinding disease.”