Researchers at Case Western Reserve University School of Medicine have been awarded a $1.57 million renewal grant from the National Eye Institute (NEI) of the National Institutes of Health to continue their study of corneal infections, specifically, bacterial keratitis, associated with contact lens wear. The grant will extend the work initiated last year with the receipt of a $2.4 million, five-year grant from the NEI.
The funding will support for four years the work of Eric Pearlman, Ph.D., professor and research director in the Department of Ophthalmology and Visual Sciences, as well as two postdoctoral investigators and one student working toward a Ph.D. The researchers hope to discover specific toll-like receptor (TLR) antagonists to regulate corneal inflammation, which could lead to the development of novel anti-inflammatory medications that could serve as alternatives to steroids to treat the infections.
Bacterial keratitis is a serious cause of visual impairment not only in the United States but also worldwide, and contact lens wear is a major risk factor for the infection in the cornea, the clear covering over the front part of the eye.
"Organisms can infiltrate an intact cornea of a lens-wearer, and a biofilm can form on the contact lens," Dr. Pearlman says. Although correctly performed cleaning of contact lenses can remove the biofilm, or aggregation of micro-organisms, he adds, "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 grant, 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.
Dr. Pearlman is the principal investigator leading a multidisciplinary team investigating fungal and bacterial keratitis that 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 Department of Ophthalmology and Visual Sciences is part of the Visual Sciences Research Center, which encompasses more than 40 vision researchers in 18 departments at Case Western Reserve University and University Hospitals Case Medical Center campus, including pharmacology, pathology, molecular biology, epidemiology and biostatistics, chemistry and biomedical engineering.
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