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
Potential Roles Of 5-hydroxytryptamine In Diseases Affecting The Colon
Funder
National Health and Medical Research Council
Funding Amount
$346,018.00
Summary
The overall aim of this project is to examine the biological roles played by 5-hydroxytryptamine (5-HT) in the human colon. 5-HT is a naturally occurring substance of the body, normally involved in controlling many body activities. Relevance is placed in this project on the possibility that 5-HT is involved in causing or contributing to certain clinical conditions, either by excess or deficiency. The conditions that are the focus of this project are chronic constipation, diverticular disease and ....The overall aim of this project is to examine the biological roles played by 5-hydroxytryptamine (5-HT) in the human colon. 5-HT is a naturally occurring substance of the body, normally involved in controlling many body activities. Relevance is placed in this project on the possibility that 5-HT is involved in causing or contributing to certain clinical conditions, either by excess or deficiency. The conditions that are the focus of this project are chronic constipation, diverticular disease and irritable bowel syndrome. It is a matter of concern that there are no specific treatments for these conditions to date, hence the thrust of the project is to increase knowledge in this area, so hopefully treatments will be developed. Our Pharmacology research group is recognised for its experience in defining drug effects on the intestine and in characterising the target sites on which they act. This has been achieved by using an integrated approach whereby different functional methods reliably detect effects at the levels of the muscle layers, the nerves that supply them and at the absorptive surface using experimental animals. In addition, the use of isolated pieces of human colon obtained from discarded operation material has been an invaluable inclusion into this process. This has allowed us to establish that 5-HT has a target site in the muscle of the colon and that this leads to relaxation and inhibition of the normal spontaneous contractile activity, said anecdotally to be abnormally high in patients with irritable bowel syndrome. We now wish to apply this expertise and knowledge to test whether 5-HT is involved in causing chronic constipation and diverticular disease and to design a drug that would be expected to be of value in treating patients with irritable bowel syndrome.Read moreRead less
Inductive Interactions Between Lens And Optic Cup Specify Cell Fates
Funder
National Health and Medical Research Council
Funding Amount
$265,500.00
Summary
Normal eye development depends on interactions between embryonic eye tissues. In the front part of the eye inductive interactions between lens and optic vesicle are important for the formation and growth of lens, ciliary body and iris. Our recent studies indicate that a family of developmentally important growth factors, the Wnts, plays key roles in this process. Our proposed studies will examine, for the first time, the role of Wnts in lens, ciliary body and iris development. Specific experimen ....Normal eye development depends on interactions between embryonic eye tissues. In the front part of the eye inductive interactions between lens and optic vesicle are important for the formation and growth of lens, ciliary body and iris. Our recent studies indicate that a family of developmentally important growth factors, the Wnts, plays key roles in this process. Our proposed studies will examine, for the first time, the role of Wnts in lens, ciliary body and iris development. Specific experimental outcomes will show if Wnts are important in promoting the formation and maintenance of the front part of the lens, the lens epithelium. The outcomes will also give us information on the molecules that mediate the effects of Wnts on lens cells and if regulatory factors from the lip of the optic cup-ciliary body can influence the pathways by which Wnts can influence the lens cells. In addition we will learn if lens-derived Wnts have a role in the formation of ciliary body and iris. Identifying factors that regulate the formation of eye tissues is fundamental to understanding the molecular basis of eye disease. For example, cataract is the most common cause of blindness in the world. Cataract surgery is the most common surgical procedure and is placing an ever-increasing burden on health care budgets. Cataracts that most commonly require surgery usually involve abnormal growth and behaviour of lens cells such as occurs in posterior subcapsular cataract and posterior capsular opacification (also known as aftercataract because it occurs subsequently to cataract surgery). Identifying molecules and mechanisms that are involved in normal formation and growth of lens cells is fundamental to understanding these diseases. In addition, as it is well known that the lens is required for the normal formation of the front part of the eye, including the ciliary body and iris, results from this study may also shed light on some developmental abnormalities such as small eye.Read moreRead less
Predictors Of Cardiovascular Disease Mortality In The Melbourne Collaborative Cohort Study
Funder
National Health and Medical Research Council
Funding Amount
$350,544.00
Summary
The Melbourne Collaborative Cohort Study was set up in the early 1990s to investigate prospectively the role of diet and other lifestyle factors in causing common chronic diseases including common cancers and cardiovascular disease. Between 1990 and 1994, 41,500 people, aged 40-69 were recruited into the MCCS. About 30% of the cohort are southern European migrants to Australia who were deliberately over-sampled to extend the range of dietary and lifestyle exposures. Migrants from southern Europe ....The Melbourne Collaborative Cohort Study was set up in the early 1990s to investigate prospectively the role of diet and other lifestyle factors in causing common chronic diseases including common cancers and cardiovascular disease. Between 1990 and 1994, 41,500 people, aged 40-69 were recruited into the MCCS. About 30% of the cohort are southern European migrants to Australia who were deliberately over-sampled to extend the range of dietary and lifestyle exposures. Migrants from southern Europe have an adverse risk factor profile in relation to obesity, body fat distribution, physical activity patterns, diabetes, smoking, blood pressure and cholesterol levels, yet their death rates from heart disease are 30-40% lower than the Australian average. A major objective of this study is to investigate the possibility that particular aspects of the diet and cuisine of migrants from southern Europe (olive oil as the major dietary fat, and high intakes of a variety of vegetables and fruit) protect against heart disease and stroke by providing high levels of a wide range of natural antioxidants. It represents the most comprehensive prospective study of diet and cardiovascular disease mortality ever conducted in Australia. A particularly powerful feature is the combination of detailed self-reported dietary intake, the very wide range of exposures to dietary factors implicated in CVD (as risk factors or protective agents), and the objective markers of dietary intake (biochemical markers of dietary intake patterns in blood collected at recruitment, body weight, body fat and body fat distribution). The data should provide a strong rationale for specific dietary recommendations as part of population-based strategies to reduce the incidence of premature mortality from heart disease and stroke in the Australian population.Read moreRead less
Physiological Mechanisms Of Efficacy Of Cervical Flexor Muscle Retraining
Funder
National Health and Medical Research Council
Funding Amount
$264,750.00
Summary
Neck pain is a significant problem in society and its frequency is beginning to match the proportions of back pain, probably reflecting our increasingly sedentary lifestyles. Several problems have been identified in the muscle system in persons who suffer from neck pain. Therapeutic exercise has been found to have benefit in preventing and relieving pain and improving the neck function. Currently there are several, quite different methods of exercise and there is controversy regarding how therap ....Neck pain is a significant problem in society and its frequency is beginning to match the proportions of back pain, probably reflecting our increasingly sedentary lifestyles. Several problems have been identified in the muscle system in persons who suffer from neck pain. Therapeutic exercise has been found to have benefit in preventing and relieving pain and improving the neck function. Currently there are several, quite different methods of exercise and there is controversy regarding how therapeutic exercise works. It has been argued that parameters such as changes in muscle strength, endurance, joint position sense or muscle coordination may be responsible for the clinical efficacy. It is difficult to disentangle the effective component of exercise strategies and thus prescribe the most effective exercise strategies. This series of experiments will evaluate the physiological factors that change with a specific exercise intervention and to compare different exercise modalities in order to identify the most effective means to induce these changes. Cervical muscle training, using a proven exercise intervention strategy for chronic neck pain and headache, has been chosen as the model to investigate these questions. This exercise strategy has been chosen not only because it has been shown to be effective, but also because it does not conform to contemporary rationales for strength or endurance training. Thus while effective in relieving pain, it is unlikely to produce changes in these parameters. Thus other mechanisms are likely to be responsible for the clinical change. This research stands to make a significant contribution to exercise therapeutics by identifying the effective components of different exercise methods and investigating the pain relieving effects of the specific exercise. This knowledge will lead to the construction of a research based exercise program for neck pain patients, rather than have the current situation of often arbitrary choice of exercise.Read moreRead less
The Effect Of Loading On The Size, Shape And Strength Of Cortical Bone During Different Stages Of Maturation
Funder
National Health and Medical Research Council
Funding Amount
$180,000.00
Summary
Osteoporosis is a condition in which the skeleton becomes fragile and susceptible to fractures. It is a public health problem that affects both men and women over the age of sixty. Although osteoporosis affects the elderly, the most opportune time to prevent osteoporosis may be during childhood. Physical activity is a lifestyle factor known to affect the strength of the skeleton. Bone density is commonly used as a measure of bone strength because it is easily measured and is related to the break ....Osteoporosis is a condition in which the skeleton becomes fragile and susceptible to fractures. It is a public health problem that affects both men and women over the age of sixty. Although osteoporosis affects the elderly, the most opportune time to prevent osteoporosis may be during childhood. Physical activity is a lifestyle factor known to affect the strength of the skeleton. Bone density is commonly used as a measure of bone strength because it is easily measured and is related to the breaking strength of bones. However changes in the shape of bones can also affect bone strength with or without an increase in bone density. Changes in bone shape in response to exercise in children or adults have rarely been investigated, and little is known about the effects of exercise on bone shape during different stages of growth. This study is the first to investigate how exercise during childhood may affect bone strength by changing bone shape. 45 elite female tennis players aged between 6 to 18 years have completed two years of this study. 90 novice and competitive male tennis players aged between 6 to 20 years and 60 healthy age matched controls will be asked to participate in this study. Measurements will be made annually for three years. The bone shape and density of the dominant and non-dominant arms of the players will be compared with the children who don't play tennis - comparisons will also be made between i) different stages of puberty and ii) girls and boys. The findings of this study are important because the lifestyle of children today may predispose them to a greater risk of osteoporosis late in life. Physical activity may be the most important modifiable protective factor against fragile bones in old age. The findings of this study will be the first to provide insight into whether there is a unique time during growth when exercise will result in the greatest increase in bone strength by changing bone shape.Read moreRead less
Sunscreen Immune Protection Factor Prediction Of Inhibition Of Anti-tumour Immunity And Carcinogenesis
Funder
National Health and Medical Research Council
Funding Amount
$186,372.00
Summary
Despite sunscreens having been used in Australia for more than 25 years the incidence of skin cancer continues to increase. This is partly due to the long lag time in developing a skin cancer, so that the current incidence reflects sun exposure patterns of many years ago. However this is also partly due to sunscreens not being as effective at preventing skin cancer as they are at preventing sunburn. The ultraviolet wavelengths found in sunlight are the prime cause of skin cancer. Australians are ....Despite sunscreens having been used in Australia for more than 25 years the incidence of skin cancer continues to increase. This is partly due to the long lag time in developing a skin cancer, so that the current incidence reflects sun exposure patterns of many years ago. However this is also partly due to sunscreens not being as effective at preventing skin cancer as they are at preventing sunburn. The ultraviolet wavelengths found in sunlight are the prime cause of skin cancer. Australians are exposed to high levels of sunlight, and consequently 66% of Australians develop skin cancer throughout their lifetime. For this reason, Australia has been dubbed the Skin Cancer Capital of the World. To reduce the incidence of skin cancer in Australia, it is recommended that individuals use sunscreens. The means of assessing the effectiveness of sunscreens is based on an SPF system, which measures the ability of sunscreens to prevent sunburn (erythema). However sunburn is induced by particular ultraviolet wavelengths, and may not be as important for skin cancer assessment as other damaging effects of sunlight, such as immunosuppression and genetic mutations. Sunscreens should be tested for protection from immunosuppression as well as sunburn, as this would aid the development of better sunscreens. We have developed the technology to measure protection of the immune system, and intend to investigate the usefulness of this new sunscreen test.Read moreRead less
Network Interactions Between Cardiovascular Control Neurons In The Brainstem Underlie Sympathetic Tone
Funder
National Health and Medical Research Council
Funding Amount
$268,328.00
Summary
High blood pressure is a very significant risk factor for many common cardiovascular diseases. Blood pressure is normally tightly regulated by groups of neurons in the brainstem; although we know that this part of the brain becomes dysfunctional in patients with high blood pressure, we do not understand why. We have recently discovered that cardiovascular control neurons can influence each other. The project will determine the effect of such communication in the control of blood pressure.