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
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
Roles For MAPK-ERK1-2, -catenin-TCF And Smad3 Mediated Signalling Pathways In TGF -induced Cataract
Funder
National Health and Medical Research Council
Funding Amount
$339,071.00
Summary
Posterior capsular opacification (PCO) is a common and costly complication of cataract surgery that is caused by aberrant growth of lens cells. The TGF growth factor family causes PCO. TGF activates three signalling pathways in the lens, MAPK-ERK1-2, -catenin-TCF and Smad3; however currently we do not know which one induces PCO. This project will identify the pathway(s) that prevent TGF from causing cataracts. This is critical for the development of pharmaceuticals to prevent PCO.
Expression And Role Of Integrins During Lens Development And Cataractogenesis
Funder
National Health and Medical Research Council
Funding Amount
$336,760.00
Summary
Cataract is the leading cause of blindness in the world. Numerous risk factors for cataract have been identified, but little is known about the cellular and molecular mechanisms that underlie this debilitating disease. Development of adequate treatments or, eventually, a cure for cataract will require a better understanding of the basic molecular mechanisms that regulate normal lens development and the formation of cataract. The research outlined in this application builds upon our previous rese ....Cataract is the leading cause of blindness in the world. Numerous risk factors for cataract have been identified, but little is known about the cellular and molecular mechanisms that underlie this debilitating disease. Development of adequate treatments or, eventually, a cure for cataract will require a better understanding of the basic molecular mechanisms that regulate normal lens development and the formation of cataract. The research outlined in this application builds upon our previous research, which has identified molecules (growth factors) that are involved in either the regulation of normal lens development and growth (FGF and TGF-beta) or the induction of cataractous changes in the lens epithelium (TGF-beta). The studies are directed at identifying members of an important family of cell adhesion molecules, the integrins, in the lens and examining the role that these molecules play in controlling lens structure and function. These cell surface glycoproteins function in adhesion of cells to each other and to extracellular matrix, and transmit signals in response to changes in the extracellular environment. Such responses include cell proliferation, migration and differentiation. In this regard they often act in concert with growth factor receptors (eg. FGF and TGF-beta). After defining where and when integrins are expressed in the developing lens we will investigate their function in mediating various lens cell responses by using genetic manipulations to alter the expression of integrins or their intracellular signaling mediators in lenses of transgenic mice. In addition, a lens explant culture system will be used to investigate the roles integrins play during lens development and during formation of anterior subcapsular cataract by TGF-beta. These studies will provide important insights into the molecular mechanisms that control cellular events in normal and abnormal lens development.Read moreRead less