Characterising Protein And Membrane Changes In Age-related Cataract Lenses.
Funder
National Health and Medical Research Council
Funding Amount
$441,624.00
Summary
Cataract is the major cause of blindness worldwide. At present the only treatment for cataract, is surgery. This, however, is associated with complications (e.g. posterior capsule opacification), is expensive (a major component of the Health budget) and cannot keep pace with the incidence of cataract in developing nations. In addition, due to the greying of the community , this problem will be of increasing importance in the future. For prevention, we need to understand why cataract develops.
I am an Opthalmologist specialising in the treatment of glaucoma and genetic eye diseases. I am trained in Molecular Genetics and researching the genetic causes of eye diseases, and how understanding the basis of disease will lead to improved outcomes.
Translational Clinical Research In Major Eye Diseases (TCR-Eye)
Funder
National Health and Medical Research Council
Funding Amount
$2,552,355.00
Summary
The four eye diseases that cause the majority of vision loss in Australia, age-related macular degeneration, diabetic retinopathy, cataract and glaucoma, impose a significant socio-economic burden, costing our nation -$lo billion a year. This CCRE will fund a world leading, broad-based, clinical and translational research program in Melbourne and Sydney to tackle these eye diseases. The new knowledge and innovative clinical strategies developed in this CCRE will impact on clinical ophthalmology ....The four eye diseases that cause the majority of vision loss in Australia, age-related macular degeneration, diabetic retinopathy, cataract and glaucoma, impose a significant socio-economic burden, costing our nation -$lo billion a year. This CCRE will fund a world leading, broad-based, clinical and translational research program in Melbourne and Sydney to tackle these eye diseases. The new knowledge and innovative clinical strategies developed in this CCRE will impact on clinical ophthalmology and the practice of other medical disciplines.Read moreRead less
Analysis Of FGF Receptor Signalling Involved In Lens Cell Proliferation And Differentiation
Funder
National Health and Medical Research Council
Funding Amount
$343,028.00
Summary
Cataract, the loss of transparency of the eye lens, is the leading cause of blindness in the world. An eventual cure for cataract depends on a better understanding of the basic molecular processes in the normal and cataractous lens. Our research has focussed on identifying the molecules that control the formation and maintenance of the lens. Growth factors are important regulators of cell behaviour and our studies have provided compelling evidence that members of the FGF growth factor family pla ....Cataract, the loss of transparency of the eye lens, is the leading cause of blindness in the world. An eventual cure for cataract depends on a better understanding of the basic molecular processes in the normal and cataractous lens. Our research has focussed on identifying the molecules that control the formation and maintenance of the lens. Growth factors are important regulators of cell behaviour and our studies have provided compelling evidence that members of the FGF growth factor family play pivotal roles in lens developmental biology by influencing lens cell proliferation and differentiation. An important finding from our laboratory is that FGF induces lens epithelial cell proliferation and differentiation at different concentrations. The FGFs elicit intracellular responses upon binding to and activating cell surface FGF receptors (FGFRs). The FGFRs are membrane bound tyrosine kinases which upon activation, activate specific signalling pathways leading to a specific cellular response. To understand how FGFs mediate and regulate different responses in lens cells, namely cell proliferation and fibre differentiation, we plan to examine the role of FGFRs in normal lens development using genetically altered FGFRs that will be expressed specifically in lenses of transgenic mice. While it is known that four different FGF receptor genes are expressed by the normal developing lens, it is unknown what role each of these play in the process of lens cell proliferation and differentiation. In addition, as we can reproduce a specific FGF-induced lens cellular response in vitro, we will use our lens explant culture system to dissect the signalling pathway(s) downstream from specific receptor activation and correlate this with a specific cellular response. By identifying the molecules and mechanisms that control the cellular processes essential for normal lens development, we can better understand how disruptions of these processes lead to cataract formation.Read moreRead less
Understanding The Genetic Determinants Of Central Corneal Thickness And Its Functional Role In Glaucoma Pathophysiology
Funder
National Health and Medical Research Council
Funding Amount
$297,263.00
Summary
Glaucoma is a common cause of blindness and visual diability in Australia. It is caused by a combination of environmental and genetic factors. People with a thin cornea (the clear covering at the front of the eye) are at increased risk of glaucoma. We are investigating the biological link between the cornea and glaucoma as well as identifying genes that determine corneal thickness. Some of these genes may also cause glaucoma. Understanding this will lead to better diagnosis and treatment.
Generation And Characterisation Of An Animal Model For Age-related Macular Degeneration
Funder
National Health and Medical Research Council
Funding Amount
$226,650.00
Summary
Age-Related Macular Degeneration (AMD) is the leading cause of irreversible blindness in the aged population in the developed world, and it is one of the least understood retinal diseases. AMD is a slow, progressive and painless condition that affects the macula, the small central part of the retina that allows one to see fine detail clearly. With the ever-increasing human life expectancy, the prevalence of AMD (15-30%) in the age group of over 75 years will significantly increase, causing enorm ....Age-Related Macular Degeneration (AMD) is the leading cause of irreversible blindness in the aged population in the developed world, and it is one of the least understood retinal diseases. AMD is a slow, progressive and painless condition that affects the macula, the small central part of the retina that allows one to see fine detail clearly. With the ever-increasing human life expectancy, the prevalence of AMD (15-30%) in the age group of over 75 years will significantly increase, causing enormous social and financial problems for the community. In spite of the significance of this problem, the exact cause of AMD is not yet known, and there is no permanent effective treatment or cure for the condition. One of the major obstacles hindering any advances towards the development of intervention strategies or therapies is the lack of an appropriate animal model. Currently, the animal models that are available for ocular diseases do not fit the human AMD situation. This project aims to characterize the first animal model for retinal degeneration caused by abnormal functioning of the retinal pigment epithelial cells (RPE). The main role of RPE cells is the phagocytosis and digestion of the continuously growing and shed light receptor segments in the eye. Their normal functioning therefore is vital to maintaining good vision. The availability of such an animal model will allow us to learn more about the changes that might occur in the eye leading to the development of AMD and to design strategies to prevent or delay progression of the condition.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.
Receptor-mediated Actions Of Prorenin In Diabetic Retinopathy
Funder
National Health and Medical Research Council
Funding Amount
$733,841.00
Summary
Despite improvements in patient care, the incidence of diabetic retinopathy is dramatically increasing. Recent evidence suggests that a component of a hormonal system, called prorenin, may participate in the development of diabetic organ disease. We will evaluate the role of prorenin in vascular and nerve damage in animal models of diabetic retinopathy. We will determine if a new inhibitor of prorenin, prevents retinal injury and is a potential treatment for diabetic retinopathy.
MULTI-CENTRED CLINICAL EVALUATION OF A NOVEL KERATOPROSTHESIS
Funder
National Health and Medical Research Council
Funding Amount
$515,091.00
Summary
The prosthesis developed by applicants, known also as Chirila keratoprosthesis, is an artificial implantable device designed to replace a diseased cornea or a failed corneal graft, and can be used in patients with no hope for a conventional replacement of the cornea with donor tissue. The device may ultimately find a wider application, as it has the potential to give better visual results than human donor grafts. Even when not rejected, the donor grafts may lead to problematic healing patterns a ....The prosthesis developed by applicants, known also as Chirila keratoprosthesis, is an artificial implantable device designed to replace a diseased cornea or a failed corneal graft, and can be used in patients with no hope for a conventional replacement of the cornea with donor tissue. The device may ultimately find a wider application, as it has the potential to give better visual results than human donor grafts. Even when not rejected, the donor grafts may lead to problematic healing patterns and astigmatism, both limiting the final vision of patients. From the 45 million blind people worldwide, at least 10 million are due to corneal diseases or trauma. The figures released by WHO suggest a doubling of this number by year 2020. Many countries are unable to provide sufficient donor corneas, sometimes for cultural-religious reasons. In developed countries, the replacement with donor tissue is a common procedure, but many patients remain untreated because their prognosis for successful grafting is poor. Figures released in Australia show that long-term success of donor transplantation is unlikely in the patients identified as high-risk recipients. Furthermore, even technically successful cases show disppointing final vision. The significance of the applicants' artificial cornea is that allows high-risk, or otherwise untreatable corneal blind patients, to have their vision restored, and it could ultimately reduce the need for donor corneal tissue. A phase I pilot study has been completed, and Phase II is currently underway with support from NH and MRC. These studies showed that the Chirila KPro is an effective means of reversible replacement of a diseased cornea.The proposed Phase III will evaluate both safety and effectiveness in different categories of patients in comparison with published outcomes of donor grafting, and will establish unequivocally the clinical potential of this prosthesis.Read moreRead less
Identification And Characterisation Of Novel Genes For Congenital Cataract
Funder
National Health and Medical Research Council
Funding Amount
$432,750.00
Summary
Cataracts are the leading cause of blindness worldwide. The term describes a clouding of the lens which may lead to visual impairment. Congenital cataracts (present at birth) are less common than age-related cataract but the lifelong impact on vision can be severe, with a third of patients remaining legally blind. Late complications such as aphakic glaucoma may be blinding. We have shown that congenital cataracts are often inherited and have performed a population-based study in South-Eastern Au ....Cataracts are the leading cause of blindness worldwide. The term describes a clouding of the lens which may lead to visual impairment. Congenital cataracts (present at birth) are less common than age-related cataract but the lifelong impact on vision can be severe, with a third of patients remaining legally blind. Late complications such as aphakic glaucoma may be blinding. We have shown that congenital cataracts are often inherited and have performed a population-based study in South-Eastern Australia over the past 5 years to determine the causative genes. A large number of families have been involved in the study and solid progress has been made in identifying mutations in cataract genes and understanding what effect these may have on the patient's prognosis. We have recently identified a new gene in a large Australian family with a syndrome of cataract, mental retardation and teeth problems. This syndrome, known as Nance-Horan syndrome was originally described in Australia 30 years ago and we have worked with the original family to find the exact gene responsible. We already know that this gene causes the same syndrome in other families and in this project we will examine whether it can cause cataract without the other features or mental retardation without cataract. We will perform a series of experiments to learn what this gene does and how it causes the disease. We have also selected 3 other very interesting families with congenital cataracts for further study as we either know already or strongly suspect that they will enable us to identify further new genes for cataract, and in one case mental retardation. Our work in other diseases indicates that understanding the genes in severe young onset cases can give valuable clues to the causes of age-related forms and may in the future enable new ways to prevent and treat the commonest cause of worldwide blindness.Read moreRead less