Professor, Center for Global Health & Diseases
Ph.D. 1992 Microbiology
University of Texas at San Antonio
RESEARCH
PROJECT 1: IMMUNOPATHOGENESIS OF OCULAR ONCHOCERCIASIS (RIVER BLINDNESS)
Parasitic filarial nematodes infect over 200 million individuals worldwide, causing debilitating inflammatory diseases such as river blindness and lymphatic filariasis. Rickettsia - like Wolbachia bacteria are essential symbionts of the major pathogenic filarial nematode parasites of humans, including Onchocerca volvulus, which causes river blindness. Using a murine model in which soluble O.volvulus antigens are injected into the corneal stroma, we reported in Science that Wolbachia play an essential role in the pathogenesis of Onchocerca keratitis, primarily by mediating neutrophil recruitment to the corneal stroma (Science, 2002. 295:1892). Immuno-gold labeling of the major Wolbachia Surface Protein show numerous bacteria both in the worms and in neutrophil vacuoles, indicating that Wolbachia are ingested by neutrophils and are therefore likely to have a role in neutrophil activation in the corneal stroma. Our studies examine the interaction between Wolbachia and neutrophils that lead to corneal disease, and the molecular events that regulate neutrophil migration through the extracellular matrix (ECM) of the corneal stroma from the limbus to the central cornea. We are also examining the role of Toll Like Receptors (see below) in development of onchocerca keratitis, and in regulation of T cell and antibody responses to Wolbachia and to filarial antigens.
PROJECT 2: TOLL LIKE RECEPTORS IN BACTERIAL KERATITIS
Bacterial keratitis is a leading cause of blindness and visual impairment in the developing and industrialized world. Trauma, ocular surface disorders, inappropriate contact lens wear and suture abscess post corneal surgery are among the causative factors that lead to breakdown of corneal defense mechanisms and facilitate access of bacteria and bacterial products into the deeper epithelial and stromal layers. Bacterial products such as lipopolysaccharide (LPS), peptidoglycan (PGN) and unmethylated bacterial DNA (CpG DNA) then activate specific Toll-like receptors (TLR) on resident corneal cells. TLRs initiate a cascade of intracellular signaling events resulting in NFkB translocation into the nucleus, and transcription of pro-inflammatory and chemotactic cytokines. LPS from most Gram negative bacteria activate TLR4, PGN from gram positive bacterial activate TLR2, and CpG DNA activates TLR9. These studies will elucidate how signals from TLRs and cytokines integrate in regulating the development and severity of bacterial keratitis. A related project is examining novel therapeutic agents directed at the Toll Like Receptor signaling pathway.
CONTACT INFORMATION
Office Phone: 216-368-1856
e-mail: eric.pearlman@case.edu
PUBLICATIONS
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