Dr. Eric Pearlman

INNATE IMMUNE RESPONSES IN FUNGAL INFECTIONS OF THE EYE
Fusarium and Aspergillus species are major causes of agriculture related and contact lens associated corneal infection in southern, humid areas of the USA, and worldwide, especially in India and China. In these regions, fungal infections are a more frequent cause of microbial keratitis than bacteria. Fusarium was also the causative organism in an outbreak of contact lens - associated keratitis in the USA and Singapore in 2005/2006 that was traced to a lens care product. As Fusarium hyphae are extremely invasive, penetrating the corneal stroma, invade the anterior chamber, and may even cause systemic disease. Because fungal keratitis is difficult to treat, both manifestations of Fusarium keratitis cause sclerosing disease that requires a corneal transplant, and in severe cases can result in loss of the eye. We use mouse models and cell cultures to examine innate immune responses that regulate growth and replication of Fusarium in the cornea, and thereby control the severity of the infection. Projects in the Pearlman laboratory will be based on identifying essential mediators of innate immunity, especially the role of Toll Like Receptors and C-type lectins such as Dectin-1 that are likely to regulate fungal replication and development of keratitis.


ROLE OF TOLL LIKE RECEPTORS IN BACTERIAL KERATITIS
The Toll Like Receptor (TLR) family of pathogen recognition molecules plays a critical role in recognizing and responding to potential pathogens, initiating anti-microbial inflammatory responses that often result in tissue damage. TLRs also respond to microbial products in the absence of live bacteria, and can induce an inflammatory response in the cornea. Proposed studies will use a new murine model of contact lens associated corneal inflammation increasing our understanding of how cells in the corneal epithelium regulate TLR responses at the molecular level. Projects in this study use murine models of TLR- induced corneal inflammation, and human corneal epithelial cells to characterize TLR signaling pathways, with the long term goal of identifying potential antagonists.


PATHOGENESIS OF ONCHOCERCA VOLVULUS KERATITIS (RIVER BLINDNESS)
River blindness caused by the filarial worm Onchocerca volvulus remains an important cause of blindness in western and central Africa. In our studies, we have examined the host innate and adaptive immune responses using a murine model in which parasite . We have focused on the role of Wolbachia bacteria, which are Richkettsia - like endosymbionts of these filarial worms. Wolbachia induce corneal disease by activating TLR2/TLR6 responses in the cornea, leading to infiltration of neutrophils to the corneal stroma. Our studies have also examined the role of adaptive immunity, and shown that TLR2 stimulation regulates IFN-gamma production, which in turn regulates the severity of the host response.

Permanent member of National Eye Institute Anterior Eye Diseases study section 2008 -2012

There are 36 million soft contact lens wearers in the USA and 140 million worldwide; therefore even a small percentage of individuals with side effects translates to a large number of patients. In addition to microbial infection of the cornea (fungal, bacterial), sterile corneal infiltrates can cause severe discomfort, leading to decreased use. Industrial relevance is therefore the use of murine model for characterization of potential anti-inflammatory agents for contact lens - associated corneal inflammation.