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.
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
Blindness exerts major physical, emotional and economic constraints and hardship upon the sufferer. Transplant surgery can restore vision to many people who are visually impaired as a result of disease affecting the front of the eye. The transplant itself is taken from the eye of a person who has died, after consent from the donor's family. Our goal is to improve the outcome for patients who require transplants of tissue to the front of the eye, in order to restore their vision or to relieve pai ....Blindness exerts major physical, emotional and economic constraints and hardship upon the sufferer. Transplant surgery can restore vision to many people who are visually impaired as a result of disease affecting the front of the eye. The transplant itself is taken from the eye of a person who has died, after consent from the donor's family. Our goal is to improve the outcome for patients who require transplants of tissue to the front of the eye, in order to restore their vision or to relieve pain. Our work is predicated on the finding that unwanted immune responses are the major cause of graft failure in such patients. The recipient recognizes the grafted tissue as being foreign, and rejects it. Treatment with conventional systemic drugs appears to hold little promise for further improvements in outcome, but gene therapy applied to the donor tissue may provide a safe and effective way of reducing transplant failure. Gene therapy can be undertaken on the donor tissue in the laboratory, prior to transplantation surgery. In this project, we will assess the suitability of a new method of modifying the transplant. All of the work will be performed on the laboratory bench, or in experimental animals.Read moreRead less
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.
Gene Transfer For Corneal Transplantation And Limbal Stem Cell Transplantation
Funder
National Health and Medical Research Council
Funding Amount
$743,463.00
Summary
The cornea is the clear window at the front of the eye. Corneal disease is the second most common reason for blindness in the world. It is sometimes made worse by additional disease affecting the ocular surface. Replacement of a damaged cornea, or of the elements that maintain a normal ocular surface, is possible by transplantation of tissue (either the cornea or the limbus) from a donor eye. The alternative, an artificial cornea, has never yet been reported to function nearly as well as does a ....The cornea is the clear window at the front of the eye. Corneal disease is the second most common reason for blindness in the world. It is sometimes made worse by additional disease affecting the ocular surface. Replacement of a damaged cornea, or of the elements that maintain a normal ocular surface, is possible by transplantation of tissue (either the cornea or the limbus) from a donor eye. The alternative, an artificial cornea, has never yet been reported to function nearly as well as does a successful corneal graft, because the interface between the patient and the prosthesis breaks down and serious problems such as infection are common. Transplantation of the cornea is very successful in some patients but in a sizable subgroup, the graft will fail because of an unwanted immune response. Rejection is the usual cause of a graft failure. Grafts to repair a damaged ocular surface also fail from rejection. Overcoming an unwanted immune response would improve the outcome of corneal transplantation by as much as thirty percent. Overcoming the twin problems of corneal graft rejection and ocular surface disease would make transplantation a feasible option for millions of blind individuals. Novel approaches to abrogation of the immune response to ocular tissue grafts are required, because the many developments in immunosuppression that have improved the survival of other types of transplants have not improved the outcome for grafts in the eye. The immunobiology of the eye is sufficiently different from that of solid organs to demand a different approach. We plan to investigate the use of localised gene transfer to donor eye tissue prior to transplantation, to improve corneal graft and limbal graft outcome.Read moreRead less
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
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.
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.