Grant to Help Case Western Reserve Team Continue Corneal Infection Research
A team of Case Western Reserve University School of Medicine researchers has received a $1.57 million renewal grant that may help bring the fuzzy area of corneal infections, especially bacterial keratitis, in contact-lens wearers into focus.
This infection in the cornea, the clear covering over the front part of the eye, is a serious cause of visual impairment. Eric Pearlman, Ph.D., professor and research director in the Department of Ophthalmology and Visual Sciences, and his team hope to discover specific toll-like receptor (TLR) antagonists to regulate corneal inflammation, which could lead to the development of anti-inflammatory medications that could serve as alternatives to steroids to treat the infections.
"Organisms can infiltrate an intact cornea of a lens-wearer, and a biofilm can form on the contact lens," Pearlman said. Although correctly cleaning contact lenses can remove the biofilm, or aggregation of micro-organisms, he added, "when one considers that 34 million people in the United States and about 140 million people worldwide wear contact lenses, even a low percentage of side effects translates into a large number of affected individuals."
The TLR family of pathogen recognition molecules plays a critical role in recognizing and responding to pathogens in the body, initiating anti-microbial inflammatory responses to them that often result in damage to tissue. In the absence of live bacteria, TLRs also respond to microbial products and can induce an inflammatory response in the cornea.
With the latest funding, the researchers will study the activation of TLR4, which is the major stimulatory component of Gram-negative bacteria, by large molecules called lipopolysaccharides, which elicit strong immune responses. They also will examine responses inside epithelial cells in the human cornea and in a murine model of corneal inflammation. The investigators' goal will be to identify potential areas on the cell surface and inside the cells that would be good targets for anti-inflammatory intervention.
Led by Pearlman, the research team also includes Mahmoud A. Ghannoum, Ph.D., E.M.B.A., professor and director of the Center for Medical Mycology in the Department of Dermatology; Loretta B. Szczotka-Flynn, O.D., M.S., associate professor of ophthalmology and visual sciences; and Arne Rietsch, Ph.D., assistant professor of molecular biology and microbiology.
The grant is from the National Eye Institute (NEI) of the National Institutes of Health.