Developing Personalised Treatment For Retinal Degeneration
Funder
National Health and Medical Research Council
Funding Amount
$262,220.00
Summary
Dr Chen seeks a clinical CDF1 to support his ambition in combining his expertise in clinical management of retinal diseases with a growing track record of clinical trials and laboratory science to develop treatment for retinal degeneration. This is achieved through a patient-centred translational platform that he has established. In the next 5 years, He will identify the most suitable method for measuring progression and develop personalised therapy for a phase I clinical trial.
Pathways To Treatment In Blinding Genetic Retinal Eye Diseases
Funder
National Health and Medical Research Council
Funding Amount
$556,956.00
Summary
Blinding eye diseases with genetic contributing factors affecting the retina or light-sensing part of the eye, damage the vision of millions of people worldwide. The vision impairment is irreversible, untreatable, and worsens with age. In this project, we will use technological breakthroughs in genome correction and sequencing, in combination with stem cell and mouse model applications, to develop pathways to treatment of these currently incurable diseases.
Self-destructing CRISPR-constructs For Targeted Genome Editing In The Retina.
Funder
National Health and Medical Research Council
Funding Amount
$679,926.00
Summary
Despite the identification of specific mutations causing many inherited retinal dystrophies, all of these conditions are currently untreatable. We have established gene-editing techniques and have developed a novel mouse model, which will serve as a robust platform for testing different techniques of gene editing in the retina. No other group in the world is known to be using this platform for gene editing and our work will expedite the clinical translation of this technology.
Gene Therapy For The Treatment Of Retinal Dystrophy In The RPE65 Knockout Mouse Using RAAV Virus Mediated Gene Therapy.
Funder
National Health and Medical Research Council
Funding Amount
$211,527.00
Summary
RPE65 is a gene that is found exclusively within the retina. At the moment the exact role of RPE65 is not known, however recent research has shown that mutations in the RPE65 gene have been found in a number of inherited retinal dystrophies (these dystrophies include Leber congenital amaurosis and autosomal recessive retinitis pigmentosa). It therefore appears that a functional, non-mutated RPE65 gene is essential for normal vision. A mouse model of RPE65-related retinal dystrophies has been rec ....RPE65 is a gene that is found exclusively within the retina. At the moment the exact role of RPE65 is not known, however recent research has shown that mutations in the RPE65 gene have been found in a number of inherited retinal dystrophies (these dystrophies include Leber congenital amaurosis and autosomal recessive retinitis pigmentosa). It therefore appears that a functional, non-mutated RPE65 gene is essential for normal vision. A mouse model of RPE65-related retinal dystrophies has been recently developed, by producing a RPE65 knockout mouse breed in which the mouse's RPE65 gene has been mutated into an inactive form. Research on these mice have shown that they develop retinal dystrophies very similar to those seen in patients with mutated RPE65 genes. We propose to use these RPE65 knockout mice to test potential methods for treating the RPE65-related retinal dystrophies in patients. In particular, we will study the potential of using gene therapy to treat these diseases. The project will involve delivering a new, functional RPE65 gene to the retinas of the RPE65 knockout mice. The new, functional RPE65 gene will then replace the inactive, mutated RPE65 gene within the mouse retinas, an action that we predict will be able to stop these mice developing retinal dystrophy. Performing such a study will allow us to improve our understanding of the RPE65-related retinal dystrophies, and provide an indication of whether they can be treated with gene therapy.Read moreRead less
A Study Of The Role Of Voltage-gated Potassium Channels In The Process Of Phototransduction, In The Setting Of Photoreceptor Sensitivity Levels And Response Times, And In The Progression Of A Distinctive Form Of Inherited Retinal Dystrophy
Funder
National Health and Medical Research Council
Funding Amount
$360,371.00
Summary
Inherited retinal disease is a major cause of blindness but the genetic basis is extremely heterogeneous. One such disorder, cone dystrophy with supernormal rod ERG, arises from mutations in KCNV2 that encodes a potassium voltage-gated channel protein. The objective of the project is to use animal models of the disease to determine the role of this channel protein in normal visual function and to assess the impact of loss of function on retinal development and function.
The Role Of Purines In Photoreceptor Death During Retinal Degeneration.
Funder
National Health and Medical Research Council
Funding Amount
$458,729.00
Summary
Abnormalities in cells at the back of the eye called photoreceptors are associated with at least 50% of all cases of blindness in this country.This project will determine whether substances released from dying photoreceptors cause the death of neighbouring cells. In addition we will examine whether treatments that block the actions of these released substances can prevent the death of photoreceptors, thereby providing a novel therapeutic agent for the treatment of devastating eye diseases.
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
Molecular Mechanisms Of Photoreceptor Protection In Rat Models Of Degenerative Retinal Disease
Funder
National Health and Medical Research Council
Funding Amount
$277,480.00
Summary
The photoreceptor cells of the eye (rods and cones) are the cornerstones of vision. Without them the complex and rich sense of vision fades into blindness. In 1 person in 4-5,000 - about 5,000 Australians and 1-2 million people world-wide - these cells degenerate spontaneously. The condition which results is known as retinitis pigmentosa (RP); it causes progesses blindness, most often affecting young adults. Despite recent advances in research, there is still no effective cure. The present work ....The photoreceptor cells of the eye (rods and cones) are the cornerstones of vision. Without them the complex and rich sense of vision fades into blindness. In 1 person in 4-5,000 - about 5,000 Australians and 1-2 million people world-wide - these cells degenerate spontaneously. The condition which results is known as retinitis pigmentosa (RP); it causes progesses blindness, most often affecting young adults. Despite recent advances in research, there is still no effective cure. The present work will explore the environmental factors which determine whether photoreceptors last the lifetime of the individual, or die prematurely. The factors which cause their premature death include genetic mutations but also include environmental factors, including the oxygen status of the retina, the brightness of light experienced and the retina's response to stress. We will investigate the mechanisms by which the retina protects photoreceptors in the face of stress, and how it prepares itself for future insults. Several of these mechanisms have already been identified. The present work will investigate their function at the molecular level, to gain the understanding need to influence their operation. Understanding the response of photoreceptors to these environmental stresses will make it possible to slow the degeneration by manipulating the retinal environment.Read moreRead less
The Cellular Organisation Of Interneurones In Human Retina
Funder
National Health and Medical Research Council
Funding Amount
$526,454.00
Summary
Our goal is to determine the numbers and types of nerve cells in the human retina: the part of the eye where visual processing starts. This data will serve as a baseline against which effects of visual disease can be measured.
Retinal Endothelial Cell Changes That Precede Retinal Vein Occlusion And The Retinal Extracellular Space Changes That Follow It
Funder
National Health and Medical Research Council
Funding Amount
$118,121.00
Summary
Dr. Min Hye Kang, at The University of Western Australia, is investigating microscopic blood vessel changes that precede the onset of devastating blindness. She is also studying functional changes that occur in the retina following deprivation of its blood supply. Her research has significantly improved our understanding of cellular mechanisms that lead to blindness. It has also aided in the development of new treatment strategies for the prevention of vision loss.