Understanding The Role Of Human Lens UV Filters In Age-Related Cataract
Funder
National Health and Medical Research Council
Funding Amount
$227,036.00
Summary
Cataract is the most common cause of blindness worldwide, The cause of cataract is currently unknown and the only treatment available at present is surgery. This represents a huge burden on the Health budgets of all developed nations, including Australia. It has been estimated that if a treatment could be developed that simply delayed the onset of cataract by 10 years, the need for surgery would be halved. The savings to the Health budget in the USA alone would be approximately $2 billion (US). ....Cataract is the most common cause of blindness worldwide, The cause of cataract is currently unknown and the only treatment available at present is surgery. This represents a huge burden on the Health budgets of all developed nations, including Australia. It has been estimated that if a treatment could be developed that simply delayed the onset of cataract by 10 years, the need for surgery would be halved. The savings to the Health budget in the USA alone would be approximately $2 billion (US). We believe, on the basis of our previous research, that human lens UV filter compounds play a major role in the protein modification that is the hallmark of age-related cataract and indeed may be the key factor in precipitating cataract. This proposal seeks to confirm this hypothesis. If this theory is confirmed, it opens the door to pharmacological intervention for cataract by, for example, treating patients (or possibly all people in middle age) with drugs that inhibit the synthesis of the UV filter compounds.Read moreRead less
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
I am an epidemiologist investigating: 1) the frequency, pathogenesis, risk factors and impacts of common age-related eye disease, particularly focused on the four leading causes of blindness: age-related macular degeneration, cataract, glaucoma and diabetic retinopathy; 2) the potential for screening and clinical diagnostic value of retinal imaging and retinal vascular signs as predictors of major systemic conditions such as hypertension, diabetes and cardiovascular disease.
Cataract Surgery And Risk Of Age-related Macular Degeneration (AMD)
Funder
National Health and Medical Research Council
Funding Amount
$339,750.00
Summary
Cataract surgery currently ranks as one of the most frequently performed and successful surgical procedures in Australia (125,000 operations-year). Age-related macular degeneration (AMD) is the principal cause of moderate visual impairment and blindness, currently accounting for blindness in between 17,300 and 30,400 Australians. Past studies have not shown a definite relationship between cataract and AMD. Follow-up data from clinical case series and from two older population-based studies (the ....Cataract surgery currently ranks as one of the most frequently performed and successful surgical procedures in Australia (125,000 operations-year). Age-related macular degeneration (AMD) is the principal cause of moderate visual impairment and blindness, currently accounting for blindness in between 17,300 and 30,400 Australians. Past studies have not shown a definite relationship between cataract and AMD. Follow-up data from clinical case series and from two older population-based studies (the Beaver Dam and Blue Mountains Eye Studies) suggested that cataract surgery might increase the risk of subsequent development of AMD in operated eyes of older persons. Such an increased AMD risk in eyes after cataract surgery appears to be both short term (observation from clinical case series) and long term (evidence from population-based studies), and persists after taking into consideration age, sex, smoking, preexisting early stage lesions of the disease and correlation between both eyes. The proposed study is to follow a large number of older patients who are undergoing cataract surgery in Western Sydney Eye Hospital and in two ophthalmologists' private rooms. Rates of subsequent development of AMD will be compared between operated and non-operated eyes, and also between the surgical cohort and the Blue Mountains Eye Study cohort. We will document macular conditions carefully before and after surgery to exclude the possibility of confounding issues. We will also investigate whether the increased risk occurs in certain subgroups of patients at high risk of AMD. If an increased AMD risk from cataract surgery is confirmed in subgroups of patients, a modified clinical practice may be indicated, to maximize cataract surgery benefit and minimize the risk of vision loss from AMD after surgery. Changes may include additional patient information and consent about this risk, delayed cataract surgery within limits of visual function, and close postoperative follow up.Read moreRead less
Probing The Structure, Mechanism And Inhibition Of Indoleamine 2,3-Dioxygenase Using Structure- And Ligand-Based Studies
Funder
National Health and Medical Research Council
Funding Amount
$319,650.00
Summary
The human enzyme indoleamine 2,3-dioxygenase (IDO) is responsible for the initiation of a major enzymatic pathway, known as the kynurenine pathway. During certain immune and infectious diseases IDO becomes over-active and this leads to accumulation of neurotoxic kynurenine pathway compounds (metabolites). The elevated levels of these metabolites have been linked to severe mental deterioration associated with diseases such as AIDS (AIDS dementia complex), malaria and Alzheimer's disease. Several ....The human enzyme indoleamine 2,3-dioxygenase (IDO) is responsible for the initiation of a major enzymatic pathway, known as the kynurenine pathway. During certain immune and infectious diseases IDO becomes over-active and this leads to accumulation of neurotoxic kynurenine pathway compounds (metabolites). The elevated levels of these metabolites have been linked to severe mental deterioration associated with diseases such as AIDS (AIDS dementia complex), malaria and Alzheimer's disease. Several kynurenine pathway metabolites have also been linked to age-related nuclear cataract, which is the major cause of human blindness. This project employs a multidisciplinary approach that brings together a team of expert scientists from medicinal chemistry, protein crystallography, protein biochemistry and neurology. The overall aims of the project are to determine the structure of IDO using the recombinant human enzyme that we have cloned and expressed in an active form and to develop compounds that will regulate levels of the kynurenine pathway metabolites by selectively inhibiting the action of IDO. In addition, we will begin to assess the medicinal value of the best inhibitors. We have already synthesised several inhibitors of IDO, but wish to design more potent inhibitors. In order to do this, computer-aided molecular modelling and X-ray crystallography (which effectively provides a picture of the enzyme with the inhibitors attached) will be used to predict the best molecular features needed for inhibition. This will greatly aid the design of new inhibitor compounds, which will then be synthesised. The best inhibitors will also be examined to determine their general pharmacological value and specifically their ability to treat AIDS dementia complex and age-related nuclear cataract. These enzyme inhibitors also have the potential to treat other significant human diseases.Read moreRead less
Autophagy Increases With Age And Obesity To Protect Against Cellular Damage And Age-related Disease
Funder
National Health and Medical Research Council
Funding Amount
$594,687.00
Summary
Waste recycling is a normal process through which cells clear unwanted material to maintain good health. There are some conditions that are associated with impaired waste recycling in cells (such as dementia), which make this process relevant to lifelong health. We have developed a new test that will, for the first time, enable accurate measurement of the recycling process 'in action' in humans, and may identify people who have poor cellular health.
Limbic Maturational Changes In Adolescence And Young Adulthood (LIMCA) - A Longitudinal Study
Funder
National Health and Medical Research Council
Funding Amount
$418,897.00
Summary
Structural and cognitive changes of the limbic regions have been linked to number psychiatric disorders. A thorough understanding of the dynamics of healthy maturation of these brain areas with age is necessary. The main aim of this research is to longitudinally study and model the neuro-developmental changes of the limbic region during adolescence and young adulthood. These will provide an invaluable template in identifying deviant patterns of limbic development in children with neuropsychiatri ....Structural and cognitive changes of the limbic regions have been linked to number psychiatric disorders. A thorough understanding of the dynamics of healthy maturation of these brain areas with age is necessary. The main aim of this research is to longitudinally study and model the neuro-developmental changes of the limbic region during adolescence and young adulthood. These will provide an invaluable template in identifying deviant patterns of limbic development in children with neuropsychiatric disorders.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