Characterizing Novel Therapeutic Interventions In A New Model Of Focal Retinopathy
Funder
National Health and Medical Research Council
Funding Amount
$536,794.00
Summary
Focal retinopathies such as age-related macular degeneration pose an immense burden on our society, both socially and economically. We have recently developed an animal model that allows us to investigate for the first time, drugs and therapies that might be used to treat AMD both after its onset, and more significantly, in at-risk populations before onset of the disease.
The Blood-Retinal Barrier - Modelling Mechanisms For Maintenance, Breakdown And Repair
Funder
National Health and Medical Research Council
Funding Amount
$394,310.00
Summary
We believe that breakdown of the barrier that separates the delicate nervous tissue of the eye from the bloodstream, the blood-retinal barrier, may be an early event in the development of age-related macular degeneration (AMD), now overall the commonest cause of blindness in Australia. We have recently demonstrated with the first scientific clinical trials to be conducted in the world that an injection of steroid into the jelly of the eye, or vitreous , of the steroid triamcinolone slows the gro ....We believe that breakdown of the barrier that separates the delicate nervous tissue of the eye from the bloodstream, the blood-retinal barrier, may be an early event in the development of age-related macular degeneration (AMD), now overall the commonest cause of blindness in Australia. We have recently demonstrated with the first scientific clinical trials to be conducted in the world that an injection of steroid into the jelly of the eye, or vitreous , of the steroid triamcinolone slows the growth of abnormal blood vessels in patients with wet AMD. In the current project, Prof Nick King, a cell biologist and viral immunologist, will collaborate with Dr Michelle Madigan, A-Prof Jan Provis, both experts in experimetnal AMD, and A-Prof Mark Gillies, a clinician-scientist specialising in AMD, to study how the treatment works using established animal and laboratory models of a damaged blood retinal barrier. We will be particularly interested in processes which are thought to critical in the development these diseases. We will also study newly described processes by which the junctions that seal the cells of the barrier together come apart. We will be interested not just in the cells that make the barrier, but also the effect of nearby cells that are thought to contribute to it. These studies will provide a solid foundation for the rationalisation of steroid treatment for AMD which can be expected to result in improved outcomes for our patients. The studies may also provide insights into how other barriers malfunction, such as the blood brain barrier which breaks down in Alzheimer s disease and multiple sclerosis.Read moreRead less
I am a medical retinal specialist who is involved in a spectrum of basic and clinical research into the cause, risk factors, prevention and treatment of age related macular degeneration, the most common cause of vision loss in Australia.
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
Identifying Novel Disease Genes In Abnormalities Of The Eye
Funder
National Health and Medical Research Council
Funding Amount
$123,454.00
Summary
The macula is located in the centre at the back of the eye and is essential for detailed and colour vision. There are familial forms of macular abnormalities and many elderly patients suffer from age-related macular degeneration. The gene function that is critical for the maintenance of a healthy macula is not fully known. In this project, a novel process in maintaining macular health will be investigated to identify the underlying genetic cause and associated functional defects.
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
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
Cellular And Molecular Mechanisms Of Human Choroidal And Retinal Vascularisation
Funder
National Health and Medical Research Council
Funding Amount
$288,210.00
Summary
The abnormal growth of new blood vessels is a major cause of blindness in people of all ages. In premature infants, changes in retinal blood vessels results in Retinopathy of Prematurity (ROP) the leading cause of infant blindness in the world. In older adults with age-related macular degeneration (ARMD), vessels in the choroid can grow into and under the retina where they can cause catastrophic loss of vision. This association of abnormal vessel growth with the most common causes of blindness h ....The abnormal growth of new blood vessels is a major cause of blindness in people of all ages. In premature infants, changes in retinal blood vessels results in Retinopathy of Prematurity (ROP) the leading cause of infant blindness in the world. In older adults with age-related macular degeneration (ARMD), vessels in the choroid can grow into and under the retina where they can cause catastrophic loss of vision. This association of abnormal vessel growth with the most common causes of blindness has motivated the search for a better understanding of how blood vessel growth in the eye is controlled in healthy tissues and how these controls fail in disease. Our proposal addresses this issue directly. Recent work shows that this neovascularization is not only a response to a rise in the local concentration of molecules that induce such angiogenesis, but also requires a fall in the levels of endogenous molecules that inhibit angiogenesis. Our study will investigate the expression of newly identified angiogenic growth factors (VEGFs) and their receptors as well as angiogenic inhibitors (VEGI and PEDF) in the developing and adult human retina and choroid. We will examine the mechanisms by which the human choroid is formed. Our preliminary results suggests the novel insight that vasculogenesis (the formation of blood vessels via transformation of vascular precursor cells) plays a major role the formation of both the human retina and choroid. Further, these exciting results suggest involvement of novel growth stimulators and inhibitors previously not known to play a role in these processes. Our studies will lead to new insights regarding the vascular growth factors and inhibitors that drive this process, thus leading to a rational basis for new therapeutic targets for the treatment of ARMD. The rapid aging of the Australian population and the consequent predicted doubling of ARMD incidence in the next 20 years demonstrates the urgency of our studies.Read moreRead less
Functional Recovery From Retinal Degeneration: Genetic, Environmental And Senescent Models
Funder
National Health and Medical Research Council
Funding Amount
$265,888.00
Summary
This project is directed towards treatment for the blindness caused by retinal degeneration. The retina of the eye degenerates in several groups of diseases, and from several causes. Many cases affect young people and result from small genetic mutations in key proteins. Many appear to be caused by environmental damage to the retina, perhaps at birth. Retinal degeneration causes progressive blindness in a minority of younger people (about 1 in 4,000, so 5,000 Australians and 1-2 million people wo ....This project is directed towards treatment for the blindness caused by retinal degeneration. The retina of the eye degenerates in several groups of diseases, and from several causes. Many cases affect young people and result from small genetic mutations in key proteins. Many appear to be caused by environmental damage to the retina, perhaps at birth. Retinal degeneration causes progressive blindness in a minority of younger people (about 1 in 4,000, so 5,000 Australians and 1-2 million people world-wide). This condition is known as Retinitis pigmentosa. However, the normal retinal undergoes a slow loss of photoreceptors whose effect is cumulative, so that the vision of all peoples slowly fades towards the blindness of old age. In this form, retinal degeneration affects potentially everyone. We have recently published an 'oxygen toxicity' theory of retinal degeneration to account for both retinitis pigmentosa and senescent degeneration. The theory applies whether the dystrophy is preciptated by genetic mutation or by environmental factors . By the time a person becomes aware of blindness (commonly night blindness) from retinal degeneration, the loss of vision results (it is argued) from 2 causes: the death of some photoreceptors (the retinal cells which detect light) and damage to surviving photoreceptors. Both death and damage are caused by oxygen toxicity, arising from particular features of the retina's metabolism and blood supply. Further, the relentless progression of the blindness is inherent in the mechanisms of oxygen toxicity. In preliminary work we have been able to slow retinal degenerations and, importantly, to restore function in degenerating retinas by countering the oxygen toxicity. Experiments are proposed to expand this evidence and explore the time course, permanence and generality of these effects. The tests of retinal recovery and stability, and the mechanisms of countering oxygen toxicity will be readily applicable to clinical trials.Read moreRead less