Properties Of Human Photoreceptors Measured Using A Scanning Laser Ophthalmoscope To Illuminate And Image The Retina
Funder
National Health and Medical Research Council
Funding Amount
$352,000.00
Summary
Vision begins with the detection of light by the rod and cone photoreceptors in the retina lining the interior of the eye. Although much is already known about the way that light is detected and the signals are processed, a great deal remains to be learned. Some of the outstanding questions could be answered using modifications to a relatively new instrument called a scanning laser ophthalmoscope (SLO) which provides images of the interior of the eye. The aims of this project are to develop a mo ....Vision begins with the detection of light by the rod and cone photoreceptors in the retina lining the interior of the eye. Although much is already known about the way that light is detected and the signals are processed, a great deal remains to be learned. Some of the outstanding questions could be answered using modifications to a relatively new instrument called a scanning laser ophthalmoscope (SLO) which provides images of the interior of the eye. The aims of this project are to develop a modified SLO, which is able to measure the levels of visual pigment (rhodopsin) in the living eye, which is also able to deliver visual stimuli to the eye, and which finally is extended to use adaptive optics so that it can image and excite individual cone photoreceptors. Using this device, we will be able to measure the regeneration of visual pigment following exposures to intense illumination, to help explain the slow recovery of visual sensitivity after intense light. We will also be able to measure the electroretinogram (ERG) from localized retinal areas, to investigate how the properties of the photoreceptor cells vary across the retina. And finally we will be able not only to visualize the individual tiny cone photoreceptors, but also to stimulate them selectively, so that we can determine the responses of the different classes of cone (red-, green-, and blue-sensitive cones) in the living human eye.Read moreRead less
Neuroprotection In A Model Of Chronic Ocular Hypertension
Funder
National Health and Medical Research Council
Funding Amount
$264,221.00
Summary
Damage can occur to nervous tissues like the retina and brain when there is a reduction in the blood supply. This can occur in the eye disease, glaucoma, in which the pressure inside the eye is elevated. This serious condition often results in blindness. Much of the neuronal damage is thought to be due to the release of an excess of glutamate. Glutamate is a chemical (neurotransmitter) that nerves use to communicate with each other, but it is toxic to nerves when present at high concentrations. ....Damage can occur to nervous tissues like the retina and brain when there is a reduction in the blood supply. This can occur in the eye disease, glaucoma, in which the pressure inside the eye is elevated. This serious condition often results in blindness. Much of the neuronal damage is thought to be due to the release of an excess of glutamate. Glutamate is a chemical (neurotransmitter) that nerves use to communicate with each other, but it is toxic to nerves when present at high concentrations. This project will utilise a new model of glaucoma to investigate the mechanisms that regulate the concentration of glutamate in the retina. If these mechanisms could be made to work more efficiently, they may prevent the build-up of the glutamate and therefore prevent damage to the nerve cells. Understanding these mechanisms will aid in the development of an effective treatment to prevent visual loss in the 150,000 Australians who suffer from glaucoma.Read moreRead less
Therapeutic Control Of Pathological Myopia: Role Of Transforming Growth Factor-beta
Funder
National Health and Medical Research Council
Funding Amount
$312,730.00
Summary
Myopia (shortsightedness) is due to the eye being too long. It is a common refractive disorder, affecting some 25-30% of people in developed countries, and results in blurred distance vision. The optical consequences of myopia, namely blurred distance vision, are correctable with spectacles or contact lenses. However, a significant minority of individuals (3% of the Australian population) have excessively long eyes and high amounts of myopia. These enlarged eyes impose abnormal stresses on the s ....Myopia (shortsightedness) is due to the eye being too long. It is a common refractive disorder, affecting some 25-30% of people in developed countries, and results in blurred distance vision. The optical consequences of myopia, namely blurred distance vision, are correctable with spectacles or contact lenses. However, a significant minority of individuals (3% of the Australian population) have excessively long eyes and high amounts of myopia. These enlarged eyes impose abnormal stresses on the structures inside, particularly affecting the retina, which is the light sensitive part of the eye. Damage that occurs to the retina in these eyes is, at present, untreatable and irreversible and can result in blindness. Myopia is the 2nd leading cause of blindness amongst adults of working age. For the eye to grow so large, its white outer coat (the sclera) must expand without allowing any leaks of the delicate structures and fluids inside. Although the sclera gets very thin as it expands, it has been shown that this process of expansion is a biochemically active process and not due to passive stretch. Before elongation of the eye can occur the biochemical structure of the sclera must change, a complex process involving accelerated production and breakdown of the biochemical building blocks of the sclera. Previous research in our laboratory indicates that changes in structure of the sclera are associated with reduced levels of the growth-controlling protein transforming growth factor-beta (TGF-beta). The aim of this project is to supplement TGF-beta levels in the sclera in order to reverse the loss of scleral tissue, stop the development of myopia and, therefore, prevent the development of the sight-threatening pathology associated with high myopia. In addition, we will determine the most effective way to deliver a sustained dose of TGF-beta to the sclera.Read moreRead less
The aim of this project is to better understand the events that cause the onset of uveitis, a common cause of visual impairment and blindness in adults. Toll like receptors (TLR) are a new group of cell surface receptors tinflammatory mediators.hat are important in immune function and the immune system's ability to recognise and respond to to microbes by recognising signature molecules contained in microbes. The TLR system is the early warning system of immune defence and activation of the TLR s ....The aim of this project is to better understand the events that cause the onset of uveitis, a common cause of visual impairment and blindness in adults. Toll like receptors (TLR) are a new group of cell surface receptors tinflammatory mediators.hat are important in immune function and the immune system's ability to recognise and respond to to microbes by recognising signature molecules contained in microbes. The TLR system is the early warning system of immune defence and activation of the TLR system induces the generation of multiple mediators that initiate and perpetuate inflammation. There has been intense interest and research into this novel family of receptors and they have been shown to play an important role in human diseases such as inflammatory bowel disease and psoriasis. The role of TLRs in uveitis has not been studied. We hypothesise that TLRs play a central role linking certain bacteria and the induction of uveitis. TLR4, a member of the TLR family has been clearly identified as the key receptor for cell wall components of gram negative bacteria (a chemical called LPS). In vitro data shows that TLR4 stimulation by LPS causes the release of inflammatory mediators. This project is designed to study the expression of TLRs in the eye, factors that control their expression and the results of stimultaing TLRs with their target chemicals. Better understanding ofd the causes and mechanisms of uveitis will allow the development of more specific and effective treatments.Read moreRead less
A Multicentre Randomised Clinical Trial Of Laser Treatment Plus Intravitreal Traimcilone For Diabetic Macular Oedema
Funder
National Health and Medical Research Council
Funding Amount
$529,500.00
Summary
A diagnosis of diabetes immediately confers a 25 fold increase in a person's risk of blindness. The macula is the vision centre of the retina, which is like the film in a camera. In people with diabetes, swelling of the macula (macular oedema) due to leakage of retinal blood vessels is the commonest cause of loss of vision. Laser treatment is proven to be helpful in reducing the risk of vision loss in eyes with diabetic macular oedema (DMO), but it does not work in 40% of cases. Injection of slo ....A diagnosis of diabetes immediately confers a 25 fold increase in a person's risk of blindness. The macula is the vision centre of the retina, which is like the film in a camera. In people with diabetes, swelling of the macula (macular oedema) due to leakage of retinal blood vessels is the commonest cause of loss of vision. Laser treatment is proven to be helpful in reducing the risk of vision loss in eyes with diabetic macular oedema (DMO), but it does not work in 40% of cases. Injection of slow release steroids is an emerging revolutionary treatment for DMO. We are the first in the world to perform a randomised clinical trial of triamcinolone injection into the eye with DMO that has failed laser treatment. A randomised clinical trial is when an equal number of eyes are randomly allocated to the treatment and placebo (no treatment) groups, so that none of the patients or the doctors knows whether each particular eye is receiving treatment or placebo. The preliminary results of our study in progress have proved that, at least in the short term, intravitreal triamcinolone (IVTA) leads to reduction of macular oedema and improved vision. We now propose a two year randomised clinical trial to test whether the combination of IVTA with laser treatment will result in a further improvement in vision in eyes with DMO. We are in a unique position to conduct such a study, having recently concluded the world's first randomised clinical trial of IVTA for wet age-related macular degeneration in 151 eyes. We have extensive experience of IVTA's significant but manageable adverse event profile. The Australian Retinal Collaboration is a group of academic retinal specialists who are committed to attaining the highest possible standards in clinical research in Australia for common blinding conditions of the retina. The results of the proposed study are likely to lead directly to a reduction of the risk of vision impairment and blindness in people with diabetes.Read moreRead less
Genetic And Molecular Basis Of Congenital Cataracts
Funder
National Health and Medical Research Council
Funding Amount
$454,510.00
Summary
Cataracts are caused when the lens of the eye (which focuses light), loses transparency. They typically occur in older individuals, but can also occur in children, even as early as from birth. They usually result in severe vision impairment which can result in complete blindness. The only treatment is invasive surgery where the outcomes are poor, particulary in very young children. This research aims to discover the genes that cause cataract in children and to investigate how cataracts form. We ....Cataracts are caused when the lens of the eye (which focuses light), loses transparency. They typically occur in older individuals, but can also occur in children, even as early as from birth. They usually result in severe vision impairment which can result in complete blindness. The only treatment is invasive surgery where the outcomes are poor, particulary in very young children. This research aims to discover the genes that cause cataract in children and to investigate how cataracts form. We are working with several large Australian families that have severe childhood cataracts in order to identify the specific genes that cause their disease. This is achieved through an investigation of the entire genome of these families which allows us to precisely pinpoint any genetic changes. We can then look for these changes in the genes in other childhood cataract patients as well as in adults with cataracts. This information will increase our understanding of how the lens of the eye works and how cataracts can form. One gene that can cause cataracts has already been identified, this is the Nance-Horan Syndrome gene. We will investigate the role of this gene in the lens of the eye. This gene also causes other severe disabilities including mental retardation. The exact function of this gene is unknown but by determining how it works we will be able to better understand cataract formation and mental retardation, with the ultimate aim of developing better diagnosis and timely treatment for these disorders.Read moreRead less
The Roles Of Beta-catenin, APC And The Wnt/beta-catenin Pathway In Lens Development And Cataract
Funder
National Health and Medical Research Council
Funding Amount
$456,764.00
Summary
Cataract is a leading cause of blindness. Many risk factors have been identified but the basic cellular and molecular mechanisms that cause cataract are not well understood. Investigation of these mechanisms is essential to identify potential targets for future therapies to arrest or prevent cataract formation. The lens is composed of epithelial and fibre cells. Much of our research has focussed on identifying genes and cell signalling pathways that regulate formation of fibre cells from the epi ....Cataract is a leading cause of blindness. Many risk factors have been identified but the basic cellular and molecular mechanisms that cause cataract are not well understood. Investigation of these mechanisms is essential to identify potential targets for future therapies to arrest or prevent cataract formation. The lens is composed of epithelial and fibre cells. Much of our research has focussed on identifying genes and cell signalling pathways that regulate formation of fibre cells from the epithelial cells. However, considerably less is known about factors that regulate formation of the epithelium itself. As the epithelial cells are affected in some types of cataract it is vitally important to understand the mechanisms that control formation and maintenance of these cells. Our previous studies have identified a growth factor family (TGF-beta) that causes epithelial cataracts. Importantly, our recent studies have identified another growth factor signalling pathway (Wnt-beta-catenin) as being essential for the formation and maintenance of the lens epithelium. We hypothesise that this pathway is disrupted dring cataract formation. This project uses state of the art tools and techniques to investigate the role of two central molecular components of this Wnt pathway (APC and beta-catenin) in the developing lens. By genetically manipulating the activity of these proteins in the mouse lens we will investigate the roles these molecules and the Wnt signalling pathway play in lens development and whether inappropriate activity results in abnormal development or cataract. We will also be able to investigate whether modulating this pathway affects the formation of epithelial cataracts by TGFbeta. The results will provide detailed information on how these molecules regulate lens structure and function and have the potential to identify targets for preventing or ameliorating cataracts.Read moreRead less
DISSECTING THE GENETICS OF GLAUCOMA AND ITS RISK FACTORS USING A TWIN STUDY.
Funder
National Health and Medical Research Council
Funding Amount
$682,850.00
Summary
Glaucoma is one of the leading causes of blindness both in Australia (affecting 2-3% of the population) and worldwide. Glaucoma is often asymptomatic until it causes permanent loss of peripheral vision that precludes 10% of individuals with the condition from holding a driver's license. Around 50% of people with glaucoma are unaware that they have the condition; therefore better screening strategies are required. Genetic factors have been shown to contribute to glaucoma and our work has revealed ....Glaucoma is one of the leading causes of blindness both in Australia (affecting 2-3% of the population) and worldwide. Glaucoma is often asymptomatic until it causes permanent loss of peripheral vision that precludes 10% of individuals with the condition from holding a driver's license. Around 50% of people with glaucoma are unaware that they have the condition; therefore better screening strategies are required. Genetic factors have been shown to contribute to glaucoma and our work has revealed that 50% of people with glaucoma have a family history of the condition. Raised intraocular pressure (IOP) is a major contributing factor in glaucoma. Although there are some genes associated with high-pressure glaucoma, little is known about the heritability of IOP itself. Optic disc cupping is another important sign in the diagnosis and management of glaucoma, but again little is known of the inheritance of this feature. Twin studies, (comparing sets of identical twins with non-identical twins); allow us to estimate the relative contribution of genetic and environmental factors to disease states or physiological measurements. Although there have been small studies involving twins with glaucoma, it is unknown to what degree the basic parameters of glaucoma diagnosis such as IOP and optic disc characteristics are heritable. This project aims to conduct a large twin study into glaucoma and its associated ocular risk factors, including refractive error. We aim to identify genes that predispose to glaucoma, which will facilitate better screening for glaucoma in family members, and the general population, and ultimately leading to improved treatment.Read moreRead less
Ultraviolet-induced Effector Molecules In Ocular Surface Diseases: Regulation Of Expression In Vitro And In Vivo
Funder
National Health and Medical Research Council
Funding Amount
$293,500.00
Summary
Pterygium is a common, recurrent, inflammatory, and sight-threatening complication of the human eye. The disease is characterised by a fleshy vascular growth that gradually covers the ocular surface if left untreated. Limbal dysplasia is a less common disease but in some regards this disease behaves much like a pterygium. We have generated considerable laboratory based data that these ocular surface disorders may be triggered by ultraviolet (UV) radiation and this fits well with the extensive ep ....Pterygium is a common, recurrent, inflammatory, and sight-threatening complication of the human eye. The disease is characterised by a fleshy vascular growth that gradually covers the ocular surface if left untreated. Limbal dysplasia is a less common disease but in some regards this disease behaves much like a pterygium. We have generated considerable laboratory based data that these ocular surface disorders may be triggered by ultraviolet (UV) radiation and this fits well with the extensive epidemiological evidence. To data the only form of treatment is surgical intervention, often with adjunctive topical agents that can cause other more severe complication of the eye. The aim of this investigation is to determine the effectiveness of agents such as retinoic acid and interferons to block or inhibit the down-stream effects of UV radiation. Currently, we have preliminary data that suggests these agents can significantly reduce several molecules that are activated by UV in cultured ocular surface cells. Furthermore, we have clinical evidence that retinoic acid and interferon can resolve both pterygia and conjunctival dysplasia in a small group of patients. If successful, these agents may replace costly and time-consuming surgical approach to treatment.Read moreRead less
An Open-label Extension Of A Randomised Clinical Trail Of Intravitreal Triamcinolone For Diabetic Macular Oedema
Funder
National Health and Medical Research Council
Funding Amount
$167,733.00
Summary
A 25 fold increase in the risk of going blind on diagnosis of diabetes is one of the most daunting threats that patients face. Most cases of vision impairment in diabetes are due to macular oedema that persists or recurs after laser treatment. There are now a number of uncontrolled, anecdotal reports that intravitreal triamcinolone (IVTA) is highly effective for the treatment of diabetic macular edema which is refractory to conventional laser treatment. We commenced the first placebo-controlled, ....A 25 fold increase in the risk of going blind on diagnosis of diabetes is one of the most daunting threats that patients face. Most cases of vision impairment in diabetes are due to macular oedema that persists or recurs after laser treatment. There are now a number of uncontrolled, anecdotal reports that intravitreal triamcinolone (IVTA) is highly effective for the treatment of diabetic macular edema which is refractory to conventional laser treatment. We commenced the first placebo-controlled, double masked clinical trial of intravitreal triamcinolone for refractory macular oedema in 2002. The 3 month results from this study provide the first scientific proof of principle that intravitreal triamcinolone reduces macular thickness and improves vision. The two year results will be available in March 2005, but confidential interim analysis of efficacy data in September 2004 suggested that the beneficial effect of triamcinolone treatment persisted. Thus it appears that treatment with intravitreal triamcinolone may be the most significant development for the prevention of blindness in people with diabetes since the introduction of laser treatment. It would also be a highly cost-effective intervention that could be administered by general ophthalmologists. The treatment cannot be recommended for routine use, however, until its long term efficacy and safety have been established. Since we already have a well studied group of patients who have received treatment for 2 years, we are in a unique position to extend the study in order to provide the long-term (5-year) safety and efficacy data that does not appear to be forthcoming from any other source. The results of this study will significantly improve knowledge of long-term outcomes of local high dose steroids for diabetic macular oedema, allowing the treatment to be used more rationally. Thus the study is very likely to directly reduce the risk of blindness in people with diabetes.Read moreRead less