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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
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.
Kidney failure is a major health disorder in Australia and with more diabetes the number of patients waiting for transplant on dialysis is increasing. Current treatments give good initial survival of the kidney transplant but most kidneys are lost due to chronic damage . We propose a number of tolerance strategies in a model of kidney transplantation that will allow transplantation without longterm immunosuppression.
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
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.
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.