Microbiology, immunology, infectious disease, corneal and tear physiology
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.
Structure and function of the tissues of the eye, ocular appendages and the central visual pathways; basic concepts of physiological, neurological, embryological, and immunological processes as they relate to the eye and vision; appreciation of the pathophysiology of various disease processes; importance of anatomy and physiology in the medical approach to ocular disease processes.
Introduction for graduate students to a general survey of the orbit, anterior and posterior segment of the eye, extraocular muscles, and neuroanatomy of the eye; vegetative physiology of the cornea and tear film, aqueous humor, crystalline lens, vitreous humor, epithelial tissue (iris, ciliary body and retina), and photochemistry.
Lower Division Course: Two hours of lecture per week. Course covers introduction to the basis of common sight-reducing visual disorders with major public health implications for society--e.g., myopia, cataracts, diabetic hypertensive eye disorders, developmental disorders (e.g., lazy eye), and environmentally induced disease and disorders (solar eye burns, cataracts). Major approaches to the prevention, diagnosis, and treatment of common disorders will be addressed in terms of the biological and optical sciences underlying the treatment or prevention. Impact of eye care on society and health and care delivery will be reviewed.