The ocular surface microbiome
We are interested in discovering whether the ocular surface harbours a unique microbiome, or whether microbes are transient colonisers from the surrounding skin. We have established that the culturable microbiota of the ocular surface is sparse and consists of low levels of coagulase-negative staphylococci and Proprionibacterium sp. that can be isolated 50% of times the ocular surface is swabbed.
Research questions that we are addressing include: (1) whether any ocular microbiome changes during contact lens wear, (2) whether any ocular microbiome is protective from colonisation by potential pathogens, (3) what is the microbiome of contact lenses, and contact lens cases and how this changes over time?
Techniques we are using include standard microbial culture and 16s rDNA sequencing.
These studies are in collaboration with Prof Ian Paulsen (Macquarie University, Sydney) and Prof Minas Coroneo (Ophthalmology, UNSW).
The ocular surface is a unique mucosal site. The cornea is an avascular tissue, and its immunological responses are different to other areas of the body. Indeed, inflammation of the cornea can be devastating, leading to scarring and vision loss. Our team investigates the role of inflammation and corneal defences during infection, particularly with Pseudomonas aeruginosa and Staphylococcus aureus.
Research questions that we are addressing include: (1) What are the different responses to infection with the Gram-negative bacterium P. aeruginosa compared to the Gram-positive bacterium S. aureus, (2) what is the role of inflammasomes in microbial keratitis, (3) what is the role of regulatory T-cells and their role in autoimmune and inflammatory eye disorders?
Techniques include the use of gene knock-out models of infection, and antibodies to control the inflammatory response.
These studies are in collaboration with Prof Matt Cooper (University of Queensland)
Development of novel surface-bound antimicrobials to combat biofilm infections
Microbes can colonise the surface of biomaterials, forming biofilms, and leading to acute and chronic infections in many areas of the body. Contact lenses are susceptible to microbial colonisation as are other medical devices such as contact lens cases, cochlear implants, catheters, implants for orthopaedics, and replacement organs. We have been studying the effect of coating materials with antimicrobial substances such as the cationic peptide melimine, quorum-sensing inhibitors and nitric oxide producing surfaces on biofilm formation. We are the first group to test in clinical trials antimicrobial surfaces on contact lenses.
Research questions that we are addressing include: (1) can surfaces be modified to prevent microbial colonisation as well as non-specific protein/lipid deposition, (2) can surfaces be modified to prevent microbial adhesion but encourage mammalian cell attachment so that the “race-to-the-surface” is won by mammalian cells, (3) do antimicrobial contact lenses reduce the indicence of keratitis during contact lens wear?
Techniques include microscopic analysis of microbial biofilm formation (confocal, AFM, electron etc), clinical trials, models of biomaterial infection.
These studies are in collaboration with Prof Naresh Kumar (UNSW; http://www.ausnano.net/index.php?page=groups&group=5302), the LV Prasad Eye Institute, Hyderabad, India and industrial sponsors.
Contact lenses and care systems
Contact lenses provide an excellent form of vision correction, and are being developed in many places to correct mypoia, presbyopia, to reduce the progression of myopia, as drug delivery devices and as sensors (e.g. for monitoring diabetes control). In order for current and new contact lenses to achieve maximum effect several issues need to be addressed. These include reducing the incidence of keratitis associated with contact lens wear (see Development of novel surface-bound antimicrobials), and improving the comfort of lenses during wear.
Research questions that we are addressing in regard to contact lens comfort include: (1) What is the role of the tear film lipid layer in contact lens discomfort, (2) how does the use of multipurpose disinfecting solutions affect ocular comfort, (3) is there a relationship between corneal sensitivty and tear film parameters during contact lens wear?
Techniques include clinical trials of contact lenses, lipidomic, proteomic and glycomic analysis of the tear film, and analysis of biochemical changes to ocular surface cells.
These studies are in collaboration with A/Prof Todd Mitchell, Dr Mike Kelso and Dr Simon Brown (University of Wollongong), Prof Tom Millar (University of Western Sydney).
The use of tears as a source of biomarkers for disease
Tears can be collected without trauma to the eye and non-invasively. Changes in tears that occur during ocular, and even non-ocular diseases, may allow us to use tears as a source of biomarkers for disease. We are currently examining changes to the biochemistry of tears to determine whether these can be used to diagnose and/or monitor dry-eye, keratoconus, and breast and prostate cancer.
Research questions include that we are addressing in these studies include: (1) do tears contain markers that allow for their use in diagnosing disease, (2) monitoring disease progression, (3) or determining effects of therapies?
Techniques include mass spectrometric analysis of the tear lipidome, proteome and glycome, as well as antibody-based biomarker discovery.
These studies are in collaboration with A/Prof Todd Mitchell, Dr Simon Brown (University of Wollongong), Dr Brad Walsh (Minomic International), Dr Valerie Wasinger (BMSF, UNSW), and A/Prof Yong Li (St. George Hospital, Sydney).