Chronic TLR9 Activation As A Mechanism For Granulomatous Reaction In The Cornea
Funder
National Health and Medical Research Council
Funding Amount
$283,416.00
Summary
Corneal opacities due to microbial infections are a major cause of blindness globally. Our novel data show that the presence of viral/bacterial DNA in the cornea induces formation of multinucleated giant cells, which are hallmarks of granulomatous reaction commonly seen in viral-induced corneal disease. Understanding the mechanisms and kinetics of macrophage differentiation in the inflamed cornea may lead to novel treatments for chronic inflammatory conditions in the eye and in other organs.
THE ROLE OF MONOCYTIC LINEAGE CELLS IN MODELS OF CORNEAL DISEASE
Funder
National Health and Medical Research Council
Funding Amount
$311,567.00
Summary
Vision relies on sharp, focused undistorted images passing through the cornea, the clear 'window' at the front of the eye. Corneal disease causes over 5 million cases of blindness worldwide. In patients who damage the delicate covering of the cornea, due to trauma or contact lens wear, there is an increased risk of infection that may lead to blindness. This project will study the ways in which immune cells in the cornea detect invasion by potential pathogens.
Mechanisms Controlling The Excitability Of Corneal Nociceptor Nerve Terminals
Funder
National Health and Medical Research Council
Funding Amount
$364,759.00
Summary
The project uses a new approach that allows, for the first time, electrical activity to be recorded and analysed from the very fine nerve endings of nerves whose activation results in painful sensations. Using this technique the mechanisms by which substances released in damaged and inflamed tissues lead to discharge of action potentials and the sensation of pain will be investigated. In particular the project investigates the role of a population of sodium ion selective pores (channels) that ar ....The project uses a new approach that allows, for the first time, electrical activity to be recorded and analysed from the very fine nerve endings of nerves whose activation results in painful sensations. Using this technique the mechanisms by which substances released in damaged and inflamed tissues lead to discharge of action potentials and the sensation of pain will be investigated. In particular the project investigates the role of a population of sodium ion selective pores (channels) that are uniquely expressed in pain sensing nerves. These channels have been hypothesised to play an important role in determining the behaviour of these nerves. In addition, the project investigates how some substances released in inflamed tissues sensitize pain sensing nerves, causing them to more readily discharge action potentials. This change is the major cause of pain associated with inflammatory diseases such as arthritis. In summary, the proposed project will provide new insight into how pain sensing nerves function. This knowledge is essential for the development of more effective strategies for treating pain resulting from inflamed and damaged tissue.Read moreRead less
The goal of our work is to improve outcomes for patients who are blind or seriously visually impaired as a result of corneal disease. Such patients can regain vision through a corneal transplant, but many such transplants fail. A corneal graft may fail because of an unwanted immune response, because blood vessels grow into the graft, or because some corneal cells die. We plan to transfer genes to the donor cornea in the laboratory, prior to corneal transplantation, to avoid such failure.
Application Of Adult Stem Cells To Bioengineered Corneal Epithelium And Endothelium Autografts
Funder
National Health and Medical Research Council
Funding Amount
$92,314.00
Summary
Damage to the cornea causes vision loss. Transplants can restore sight but carry risk of rejection and therefore require anti-rejection therapy, which has side effects. Bioengineered corneal components could replace transplants. Our goals are: 1) Growth of corneal endothelium and epithelium from adult stem cells to reduce the amount of tissue so the patient's own cells could be used. 2) Develop scaffolds that are suitable for implantation or other methods to deliver cells.
A Novel Mesenchymal Stromal Cell And Biomaterial For Corneal Reconstruction
Funder
National Health and Medical Research Council
Funding Amount
$508,611.00
Summary
Our research group has identified a new cell type (L-MSC) with the potential to treat a variety of eye diseases. We have also developed a novel material from a protein found in silk, that has potential as a vehicle for delivering healthy cells into diseased eyes. The present project will build upon these promising results by evaluating the properties of L-MSC necessary for clinical use and by testing the feasibility of our new cell delivery system.
Characterisation Of The Host Response In A Mouse Model Of Staphylococcus Aureus Keratitis.
Funder
National Health and Medical Research Council
Funding Amount
$248,850.00
Summary
Staphylococcus is the most common cause of bacterial eye infections (microbial keratitis) . This ocular infection is associated with severe pain, redness, discharge and frequently results in the loss of vision or blindness. Predisposing factors for this disease include contact lens wear and immunocompromised individuals such as those with HIV, diabetes or aged populations. S. aureus keratitis is difficult to treat using conventional antibiotics as although bacteria may be eliminated, vision loss ....Staphylococcus is the most common cause of bacterial eye infections (microbial keratitis) . This ocular infection is associated with severe pain, redness, discharge and frequently results in the loss of vision or blindness. Predisposing factors for this disease include contact lens wear and immunocompromised individuals such as those with HIV, diabetes or aged populations. S. aureus keratitis is difficult to treat using conventional antibiotics as although bacteria may be eliminated, vision loss may still result from scarring. S. aureus also causes a wide range of hospital associated infections such as pneumonia, endocarditis, bacteremia, wound infections, osteomyelitis and septic arthritis. In recent times strains of S. aureus have emerged which are multi-drug resistant including methicillin resistant S. aureus (MRSA). These may only be treated with the drug Vancomycin. However, vancomycin resistant S. aureus have been reported in both Japan and the USA. Now, the search for new treatments for this bacterium is of vital importance. This project will utilise the novel S.aureus mouse model for keratitis, which we have developed in our laboratories. Our model will enable us to investigate the host responses to bacterial infection. Existing models in the rabbit do not allow such detailed studies due to the lack of existing molecular probes and antibodies. Insights into potential adjunct therapies will also be gained. This research could lead to the development of novel therapeutic measures aimed at manipulating the host response to reduce scarring and consequent blindness. This information may also be important for the development of prophylactic treatments for those patients at high risk, such as diabetics and immunocompromised individuals of developing this disease.Read moreRead less
Regional Immunosuppression For Corneal Transplantation
Funder
National Health and Medical Research Council
Funding Amount
$268,264.00
Summary
Blindness exerts major physical, emotional and economic constraints and hardship upon the sufferer. Corneal transplantation is a well-accepted surgical treatment for visual impairment caused by opacification of the cornea, the transparent window at the front of the eye. Corneas for transplantation are retrieved from people who have recently died, after permission has been sought from the donor's family. Unfortunately, a significant proportion of corneal transplants fail because they are recogniz ....Blindness exerts major physical, emotional and economic constraints and hardship upon the sufferer. Corneal transplantation is a well-accepted surgical treatment for visual impairment caused by opacification of the cornea, the transparent window at the front of the eye. Corneas for transplantation are retrieved from people who have recently died, after permission has been sought from the donor's family. Unfortunately, a significant proportion of corneal transplants fail because they are recognized as foreign, and undergo rejection by the recipient. Once a corneal graft has failed, it is no longer transparent to light. A number of novel interventions are being developed to reduce the incidence of corneal graft rejection, but at present it is uncertain exactly how these should be delivered to the patient. The research described in this application is designed to discover how therapeutic agents and interventions can best be targeted, to prevent corneal graft rejection. Overcoming an unwanted immune response would improve the outcome of corneal transplantation by as much as thirty percent.Read moreRead less