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Home > Faculty
> Suzanne J. Fleiszig
Reseach Interests
Research in my laboratory focuses on the pathogenesis of bacterial
infections of the cornea. The principal aim of my research is to
determine why patients who wear contact lenses are prone to infectious
keratitis. These infections most often involve the bacterium Pseudomonas
aeruginosa and can lead to severe vision loss. The results of initial
studies indicated that ocular flora is altered in some contact lens
wearers and that a large proportion of patients' lens cases are
contaminated with bacteria during normal use.
However, neither of these phenomena entirely explain the pathogenesis
of infection, since in general bacteria cannot infect a healthy
cornea, even when introduced in large numbers. This implies that
there must be some form of compromise, in addition to bacterial
contamination of the eye before the infectious process can begin.
For this reason we are interested in establishing how the healthy
cornea resists infection, how contact lens wear and other predisposing
factors could compromise these defenses, and what bacterial virulence
factors are involved in initiating infection. This project involves
the study of bacterial interaction with tear film factors and the
ocular surface, bacterial adherence to cornea and contact lenses,
mechanisms of bacterial invasion and killing of corneal epithelial
cells, transcorneal migration of bacteria and disruption of normal
host tissue physiology by bacteria.
It is widely believed that in the healthy eye infection is prevented
because tear film factors are able to neutralize bacteria, and that
bacteria are not able to adhere to the cornea unless it is overtly
injured. However, the results of our studies have demonstrated that
neither of these assumptions are entirely accurate.
We have found that P. aeruginosa can survive for several hours in
tears, and that this microbe can adhere to uninjured cornea, under
certain circumstances. Other findings are that ocular mucin and
the cell surface glycocalyx protect the cornea from infection by
inhibiting bacterial adherence to underlying corneal epithelial
cells, that contact lens wear increases bacterial adherence to corneal
epithelial cells, and that P. aeruginosa - which is thought to be
an extracellular pathogen - is in fact able to invade corneal epithelial
cells.
In addition to characterizing corneal defenses and the events that
occur during infection, we are also studying the molecular mechanisms
involved in these processes with a view to developing therapeutic
and/or preventative measures.
Techniques that are being used to study bacterium/host interactions
include adherence assays, bacterial invasion and cytotoxicity assays,
microscopy (including light, fluorescence, immunohistochemistry,
scanning and transmission electron microscopy), various biochemical
assays and molecular genetics.
Although much of this work is performed using primary epithelial
cell cultures, we have developed several other models for these
studies. These include in vitro models for the study of bacterial
interaction with human corneal cells and whole cornea of rat, rabbit
and mouse, and an in vivo model for infection in mice.
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