Control Of Refractive Error Through Ionically Driven Fluid Movements
Funder
National Health and Medical Research Council
Funding Amount
$208,600.00
Summary
Myopia affects about half the world's population with recent studies suggesting epidemic proportions among some Asian schoolchildren though we are not seeing this in Australia. Costs associated with detection, monitoring and optical correction of low and high myopia are huge. High myopes (15% with > 6D) also have a greatly increased risk of blindness between the ages of 30 and 50 years due to secondary disorders associated with impaired fluid balance (retinal and choroidal oedema, macula oede ....Myopia affects about half the world's population with recent studies suggesting epidemic proportions among some Asian schoolchildren though we are not seeing this in Australia. Costs associated with detection, monitoring and optical correction of low and high myopia are huge. High myopes (15% with > 6D) also have a greatly increased risk of blindness between the ages of 30 and 50 years due to secondary disorders associated with impaired fluid balance (retinal and choroidal oedema, macula oedema, retinal detachment and glaucoma). Currently there is no accepted pharmaceutical treatment for myopia though our studies in chick have provided the theoretical rationale and experimental data for a potential therapy and patent. This patent is now at the PCT stage and attests that changes in the abundance of the ions of the subretinal space control fluid movements across the retina to choroid and can be modulated therapeutically by diuretics to control fluid flow and hence axial growth and myopia. This application aims to take our current knowledge about fluid control in myopic chick into a mammalian model prior to preclinical trials in monkey. We anticipate it will take 1 year to establish the feasibility of diuretic control of experimentally induced myopic refractive errors in guinea pigs and the best drug and best the dosage range. These studies will contribute to the scientific understanding and bring the proposed pharmaceutical therapy for myopia in adults and children to a point of full commercialization. We believe that the results found in chick will have significance for early and late-onset myopia in humans as it is highly likely that the same mechanisms of ocular growth regulation operate throughout life.Read moreRead less
The Mechanism Of Action Of Muscarinic Receptor Antagonists In Preventing Axial Myopia
Funder
National Health and Medical Research Council
Funding Amount
$242,545.00
Summary
Myopia (short-sightedness) is the most common refractive error and is due to the eye being too long and, if uncorrected, results in blurred distance vision. Approximately 30% of the population in developed countries, such as Australia, suffer from myopia. In a significant minority of individuals with high degrees of myopia, it is a sight threatening condition and a leading cause of blindness. It has been found that the pharmacological agent, atropine, is effective in preventing myopia in childre ....Myopia (short-sightedness) is the most common refractive error and is due to the eye being too long and, if uncorrected, results in blurred distance vision. Approximately 30% of the population in developed countries, such as Australia, suffer from myopia. In a significant minority of individuals with high degrees of myopia, it is a sight threatening condition and a leading cause of blindness. It has been found that the pharmacological agent, atropine, is effective in preventing myopia in children and in animal models of myopia. However the side effects of blurred vision at near, glare from dilated pupils and the unknown long term effects of chronic atropine treatment have prevented this approach to myopia control from becoming an established treatment in children. It was originally thought that the drug worked by preventing the eye from accommodating for near objects, however it has now been shown that atropine does not to work by this mechanism, but rather by another non-accommodative mechanism. The aim of this project is to determine the mechanism of action of this class of drugs (known as muscarinic antagonists) in preventing myopic eye growth. The project will investigate in which ocular tissues the various subtypes of muscarinic receptors sensitive to these drugs are located and how these are changed in myopic eyes. It will also determine the specific receptor subtype these drugs act on and whether these drugs inhibit eye growth in myopia by altered retinal signalling activity. The results from this study will elucidate the mechanism and route of action of muscarinic antagonists in preventing myopic eye growth. These findings will advance the probability of developing an effective selective muscarinic antagonist drug to use for the prevention of axial myopia without the side effects associated with the broad-band antagonist atropine. The development of such drugs will have a major economic benefit to the Australian population.Read moreRead less
The Role Of Integrins In The Regulation Of Scleral Remodelling During Pathological Myopia Development
Funder
National Health and Medical Research Council
Funding Amount
$234,750.00
Summary
Myopia (short-sightedness) 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. Most myopia is easily corrected with spectacles or contact lenses. However a small, but significant, group of individuals (in Australia, 1-2% of people) have high degrees of myopia. These enlarged eyes impose abnormal stresses on the structures inside, particularly affecting the retina which is the light s ....Myopia (short-sightedness) 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. Most myopia is easily corrected with spectacles or contact lenses. However a small, but significant, group of individuals (in Australia, 1-2% of people) have high degrees 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. Any damage that occurs to the retina in these eyes is, at present, untreatable and irreversible and can result in blindness. In fact, myopia is the 2nd leading cause of blindness amongst adults of working age. In order 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 not just due to stretching. Before any stretching can occur the biochemical structure of the sclera must change and this is a complex process, driven by the scleral cells and involving the synthesis of structural components and activity of enzymes which breakdown scleral structure. The aim of this project is to investigate the role of specific scleral proteins (integrins) in high myopia. Integrins reside on the surface of the scleral cells and communicate information about the changes going on in the surrounding sclera. We predict these proteins are important in keeping the cell informed of the local biochemical and biomechanical changes in the sclera and in driving the cell to rapidly adapt to these changes. The project will provide a greater understanding of the process of scleral thinning in high myopia and allow us to test the potential of integrins as therapeutic targets in the sclera, thereby giving us the opportunity of preventing blindness in a number of highly myopic individuals.Read moreRead less
Gene-environment Interactions In The Aetiology Of Myopia
Funder
National Health and Medical Research Council
Funding Amount
$671,285.00
Summary
The rapid rise in the prevalence of shortsightedness poses a major public health challenge. The Sydney Myopia Study has collected a large database on environmental risk factors, and has documented a major protective effect of children spending more time outdoors. Other studies suggest that myopia has a major genetic component. This study will collect DNA samples from over 4000 participants in the Sydney Myopia Study, and through genome-wide scanning, will look for gene-environment interactions.