RNA Interference In Model Systems Of Macular Degeneration.
Funder
National Health and Medical Research Council
Funding Amount
$166,500.00
Summary
Exudative age-related macular degeneration (AMD) is the most common cause of irreversible severe vision loss in the elderly, with an estimated 25-30 million people worldwide blind due to AMD. There is currently no standard treatment for AMD. A safe, specific and effective pharmacologic agent for AMD, therefore, has enormous therapeutic, social and economic benefits. AMD is underpinned by vascular leakiness and new blood vessel formation. We have demonstrated that Egr-1, a nuclear transcription f ....Exudative age-related macular degeneration (AMD) is the most common cause of irreversible severe vision loss in the elderly, with an estimated 25-30 million people worldwide blind due to AMD. There is currently no standard treatment for AMD. A safe, specific and effective pharmacologic agent for AMD, therefore, has enormous therapeutic, social and economic benefits. AMD is underpinned by vascular leakiness and new blood vessel formation. We have demonstrated that Egr-1, a nuclear transcription factor, plays a key regulatory role in a diverse array of angiogenic processes. In this project, we will use novel gene-targeting agents (Egr-1 siRNA) to provide preclinical proof-of principle evidence of their therapeutic potential in established animal models of AMD. These studies will pre-empt Phase IA safety trials in AMD patients.Read moreRead less
A Functional Predictive Test For Age-related Macular Degeneration
Funder
National Health and Medical Research Council
Funding Amount
$532,500.00
Summary
Age-related macular degeneration (AMD) is the leading cause of blindness in our community. It is a progressive, late onset disease affecting central vision. Signs of disease are present in 15% of the population over 50 years with severe visual loss affecting increasing numbers in each subsequent decade. By 90 years 25% of people will have lost significant vision. There is no prevention, and treatment options are limited and have little impact on the rates of blindness. AMD causes enormous person ....Age-related macular degeneration (AMD) is the leading cause of blindness in our community. It is a progressive, late onset disease affecting central vision. Signs of disease are present in 15% of the population over 50 years with severe visual loss affecting increasing numbers in each subsequent decade. By 90 years 25% of people will have lost significant vision. There is no prevention, and treatment options are limited and have little impact on the rates of blindness. AMD causes enormous personal costs and places a massive burden on health resources. The high prevalence, anticipated increase in the ageing population and the limited treatment options, highlight the urgency with which research is required. The early clinical signs of AMD are yellow deposits called drusen, in the central retina (macula) and alteration in retinal pigmentation. As AMD progresses the macula is damaged either through atrophy (holes) or by growth of blood vessels. Currently, clinically accessible information about drusen and pigmentary changes are used to grade the severity of disease and predict the risk of progression to vision loss. This at risk group is recruited into prevention and intervention studies looking for new interventions. Such scoring of clinical characteristics currently underpins all clinical trials and epidemiological research in AMD. However this scheme is not without limitations, and results in an inexact correlation between clinical appearance and risk of blindness. We believe that a test of retinal function, (ability to see in the dark, to detect a faint light), will provide a better correlation for identifying patients at high risk of vision loss. We aim to test various aspects of retinal function (in both the light and dark and for moving and stationary objects) in subjects with early clinical signs of AMD, to identify parameters that will be more sensitive and specific predictors of risk of progression to visually devastating complications of AMD.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
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