Professor of Optometry and Vision Science, Infectious Diseases & Immunity, and Microbiology
Vision Science 206A. Anatomy and Physiology of the Eye and Visual System
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.
Vision Science 212D. Anatomy and Vegetative Physiology of the Eye
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.
Optometry 10. The Eye and Vision in a Changing Environment
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.
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.
P. aeruginosa utilizes the type III secreted toxin ExoS to avoid acidified compartments within epithelial cells. Heimer SR, Evans DJ, Stern ME, Barbieri, JT, Yahr T, Fleiszig SMJ. PLoS One, in press.
Surfactant Protein D Contributes to Ocular Defense against Pseudomonas aeuruginosa in a Murine Model of Dry Eye Disease. Heimer SR, Evans DJ, Mun JJ, Stern ME, Fleiszig SMJ. PLoS One. 2013 Jun 6;8(6):e65797. Print 2013.
Why does the healthy cornea resist Pseudomonas aeruginosa infection? Evans DJ, Fleiszig SMJ. Am J Ophthalmol. 2013 Jun;155(6):961-970.e2. Epub 2013, Apr 17. 2013.
MicroRNA-762 is upregulated in human corneal epithelial cells in response to tear fluid and Pseudomonas aeruginosa antigens and negatively regulates the expression of host defense genes encoding RNase7 and ST2. Mun JJ, Tam C, Evans DJ, Fleiszig SMJ. PLoS One. 2013;8(2):e57850. Epub 2013, Feb 28. 2013.
Association between cytotoxic and invasive Pseudomonas aeruginosa and clinical outcome in bacterial keratitis. Borkar DS, Fleiszig SMJ, Leong C, Lalitha P, Srinivasan M, Ghanekar AA, Tam CA, Li WY, Zegans ME, McLeod SD, Lietman TM, Acharya NR. JAMA Ophthalmol. 2013 Feb;131(2):147-53, 2013.
Microbial keratitis: Could contact lens material affect disease pathogenesis? Evans DJ, Fleiszig SMJ. Eye & Contact Lens. 72-77, 39, 2013.
Cytokeratins mediate epithelial innate defense through their antimicrobial properties. Tam C, Mun JJ, Evans DJ, Fleiszig SMJ. J Clin Invest. 122 (10) 3665-3677, 2012.
Translocon-independent intracellular replication by Pseudomonas aeruginosa requires the ADP-ribosylation domain of ExoS. Hrintenko V, Evans DJ, Fleiszig SMJ. Microbes Infect 14:1366-73, 2012.
Adenylate cyclase activity of Pseudomonas aeruginosa ExoY can mediate bleb-niche formation in epithelial cells and contributes to virulence. Hritonenko V, Mun JJ, Tam C, Simon N, Barbieri JT, Evans DJ, Fleiszig SMJ. Microb Pathog, 51: 305-312, 2011.
3D quantitative imaging of unprocessed live tissue reveals epithelial defense against bacterial adhesion and subsequent traversal requires MyD88. Tam CA, LeDue J, Mun JJ, Herzmark P, Robey EA, Evans DJ, Fleiszig SMJ. PLoS ONE, 6(8): e24008, 2011.
Pseudomonas aeruginosa association with anionic hydrogel surfaces in the presence of aqueous divalent-cation salts. Tran VB, Sung YS, Fleiszig SMJ, Evans DJ, Radke CJ. Dynamics of J Colloid and Interface Science, 362: 58-66, 2011.
Modulation of epithelial immunity by mucosal fluid. Mun JJ, Tam C, Evans DJ, Fleiszig SMJ. Scientific Reports: 1,8; 2011.
Role of defensins in corneal epithelial barrier function against Pseudomonas aeruginosa traversal. Augustin DK, Heimer SR, Tam C, Li WY, Le Due JM, Evans DJ, Fleiszig SM. Infect Immun. 2011 Feb;79(2):595-605.
Factors Impacting Corneal Epithelial Barrier Function against Pseudomonas aeruginosa Traversal. Alarcon I, Tam C, Mun JJ, Ledue J, Evans DJ, Fleiszig SM. Invest Ophthalmol Vis Sci. 2011 Mar 14;52(3):1368-77.
The ADP-ribosylation domain of Pseudomonas aeruginosa ExoS is required for membrane bleb niche formation and bacterial survival within epithelial cells. Angus AA, Evans DJ, Barbieri JT, Fleiszig SM. Infect Immun. 2010 Nov;78(11):4500-10.
Pathogenesis of contact lens-associated microbial keratitis. Fleiszig SM, Evans DJ. Optom Vis Sci. 2010 Apr;87(4):225-32.
The impact of inoculation parameters on the pathogenesis of contact lens-related infectious keratitis. Tam C, Mun JJ, Evans DJ, Fleiszig SM. Invest Ophthalmol Vis Sci. 2010 Jun;51(6):3100-6.
Role of the corneal epithelial basement membrane in ocular defense against Pseudomonas aeruginosa. Alarcon I, Kwan L, Yu C, Evans DJ, Fleiszig SM. Infect Immun. 2009 Aug;77(8):3264-71.
Clearance of Pseudomonas aeruginosa from a healthy ocular surface involves surfactant protein D and is compromised by bacterial elastase in a murine null-infection model. Mun JJ, Tam C, Kowbel D, Hawgood S, Barnett MJ, Evans DJ, Fleiszig SM. Infect Immun. 2009 Jun;77(6):2392-8.
The role of twitching motility in Pseudomonas aeruginosa exit from and translocation of corneal epithelial cells. Alarcon I, Evans DJ, Fleiszig SM. Invest Ophthalmol Vis Sci. 2009 May;50(5):2237-44.
Pathogenic phenotype and genotype of Pseudomonas aeruginosa isolates from spontaneous canine ocular infections. Ledbetter EC, Mun JJ, Kowbel D, Fleiszig SM. Invest Ophthalmol Vis Sci. 2009 Feb;50(2):729-36.
Expression of surfactant protein D in human corneal epithelial cells is upregulated by Pseudomonas aeruginosa. Ni M, Tam C, Verma A, Ramphal R, Hawgood S, Evans DJ, Fleiszig SM. FEMS Immunol Med Microbiol. 2008 Nov;54(2):177-84.
Pseudomonas aeruginosa induces membrane blebs in epithelial cells, which are utilized as a niche for intracellular replication and motility. Angus AA, Lee AA, Augustin DK, Lee EJ, Evans DJ, Fleiszig SM. Infect Immun. 2008 May;76(5):1992-2001.
Mutation of the phospholipase catalytic domain of the Pseudomonas aeruginosa cytotoxin ExoU abolishes colonization promoting activity and reduces corneal disease severity. Tam C, Lewis SE, Li WY, Lee E, Evans DJ, Fleiszig SM. Exp Eye Res. 2007 Dec;85(6):799-805.
Life at the front: dissecting bacterial-host interactions at the ocular surface. Evans DJ, McNamara NA, Fleiszig SM. Ocul Surf. 2007 Jul;5(3):213-27. Review.
Human tear fluid protects against Pseudomonas aeruginosa keratitis in a murine experimental model. Kwong MS, Evans DJ, Ni M, Cowell BA, Fleiszig SM. Infect Immun. 2007 May;75(5):2325-32.
The Glenn A. Fry award lecture 2005. The pathogenesis of contact lens-related keratitis. Fleiszig SM. Optom Vis Sci. 2006 Dec;83(12):866-73.
Type III secretion-dependent modulation of innate immunity as one of multiple factors regulated by Pseudomonas aeruginosa RetS. Zolfaghar I, Evans DJ, Ronaghi R, Fleiszig SM. Infect Immun. 2006 Jul;74(7):3880-9.
Actin cytoskeleton disruption by ExoY and its effects on Pseudomonas aeruginosa invasion. Cowell BA, Evans DJ, Fleiszig SM. FEMS Microbiol Lett. 2005 Sep 1;250(1):71-6.