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
I am a glial-vascular biologist determining the cellular and molecular mechanisms of vessel formation in the retina and choroid. These studies are undertaken during normal developmental and various experimental models of pathological neovascularisation. A
New Dynamometric Techniques For Predicting Glaucoma Progression
Funder
National Health and Medical Research Council
Funding Amount
$171,825.00
Summary
Glaucoma is a major cause of blindness in our community. The biggest risk factor for glaucoma is raised intraocular pressure. However, the exact cause of the disease remains unknown. Through our basic science studies in animals we have discovered that changes in blood flow in the vessels at the optic disk may be involved in the disease process. In recent clinical trials we discovered that the presence or absence of pulsations in the retinal veins at the disk was both an indicator of severity and ....Glaucoma is a major cause of blindness in our community. The biggest risk factor for glaucoma is raised intraocular pressure. However, the exact cause of the disease remains unknown. Through our basic science studies in animals we have discovered that changes in blood flow in the vessels at the optic disk may be involved in the disease process. In recent clinical trials we discovered that the presence or absence of pulsations in the retinal veins at the disk was both an indicator of severity and progression of glaucoma. This is a major breakthrough because there is no other means of predicting in which glaucoma patients vision loss will develop most rapidly. This information will be very helpful in deciding which patients should have the most agressive treatment to restore normal intraocular pressure. This project seeks to develop a new commercial device to make such an examination easy for any clinical ophthalmologist. The device allows the doctor to examine the vessels at the disk whilst applying slight pressure to the eye to temporarily raise intraocular pressure. A footswitch is pressed when the doctor sees the vessels pulsate. The required force is recorded by a laptop computer and the data stored along with the patients details. Now we have confirmed the ability of such a measurement to predict the rate of visual field loss in glaucoma, such a measurement will become much more widespread in clinical ophthalmology, offering a new and large scale opportunity for such instrumentation. Our device will be easy to operate, more comfortable for the patient, and will be of major diagnostic value in glaucoma clinics worldwide.Read moreRead less
Childhood Retinal Characteristics: Optical Coherence Tomography And Clinical Comparisons
Funder
National Health and Medical Research Council
Funding Amount
$64,631.00
Summary
Optical Coherence Tomography (OCT) of the optic disc and retina has been introduced rapidly into clinical practice, yet there is a paucity of data on its normal distribution or its comparisons with clinical appearances as seen in photographic images. Using the extensive database of OCT and optic disc photos of a population sample of 4091 schoolchildren, influences of confounders (eye size and shape, body size, refraction) will be assessed to aid clinicians in their interpretation of OCT results.
The fovea is a specialized part of the retina which enables us to see fine detail. The fovea is characterised by an extremely high concentration of photoreceptor cells in a small, prescribed area to detect detail in the pattern of light reaching the retina. Each of these photoreceptor cells is connected to at least four other cells within the retina, which further refine the information coded by the photoreceptors. Because this circuitry involves so many cells, the retina has a tendency to be th ....The fovea is a specialized part of the retina which enables us to see fine detail. The fovea is characterised by an extremely high concentration of photoreceptor cells in a small, prescribed area to detect detail in the pattern of light reaching the retina. Each of these photoreceptor cells is connected to at least four other cells within the retina, which further refine the information coded by the photoreceptors. Because this circuitry involves so many cells, the retina has a tendency to be thick at the specialized area. However, in development the cells connected to the foveal photoreceptors move away from the central concentration of photoreceptors, still keeping their contacts with them. This results in thinning of the retina locally, so it has a volcanoe-like formation at the fovea, in which photoreceptors are concentrated within the crater and the displaced cells are accumulated on the rim. The events which trigger these cell displacements that form the fovea are unknown. We propose to investigate growth factors which signal between the fovea and the developing blood supply, and the relationship between the formation of the fovea and neuronal activity. This study will provide a new perspective on factors which affect central visual function and its vulnerability to insult in premature infants and in aging.Read moreRead less
Optical And Neural Limits Of Visual Performance In Myopia
Funder
National Health and Medical Research Council
Funding Amount
$191,902.00
Summary
Short-sightedness (myopia) is one of our most common eye problems, affecting approximately 20% of people. It is usually due to the eye becoming too long for its power. While we can correct short-sight with contact lenses, spectacles and more recently refractive surgery, recent evidence shows that the vision of corrected myopes is poorer than that of people who have good distance vision without the need for an optical correction. This reduction is present even when the optical minification of spe ....Short-sightedness (myopia) is one of our most common eye problems, affecting approximately 20% of people. It is usually due to the eye becoming too long for its power. While we can correct short-sight with contact lenses, spectacles and more recently refractive surgery, recent evidence shows that the vision of corrected myopes is poorer than that of people who have good distance vision without the need for an optical correction. This reduction is present even when the optical minification of spectacle lenses is taken into account (the lenses used to correct short-sightedness make objects look smaller). It is possible that the anatomical changes to the eye that occur in short-sightedness are the cause of the reduced vision. Even if the optics can be fully corrected with refractive surgery, as is now being proposed, this may not result in excellent vision. The anatomical changes may occur in different parts of the eye and depending on where they occur the nature of the visual reduction will vary. The location of the retinal changes may also be important in terms of eventual pharmacological treatments for short-sightedness. In addition, the significance of the visual reduction, in terms of its effect on the functioning of short-sighted people, e.g. ability to perform under less than optimal visual conditions such as in the presence of glare or reduced light levels, is not known. We plan to investigate this by identifying the optical and neural contributions to visual performance in short-sighted people.Read moreRead less
Pterygia, one of the most common ocular complaints in Australia and worldwide, are thought to originate from overexposure to UV light. We propose that UV-irradiation stimulate certain cells in the eye to produce cytokines, growth factors and enzymes which degrade scaffold proteins such as collagens. These enzymes may play a key role in the progressive and invasive nature of pterygia. Dissecting the mechanism(s) by which UV light induces these proteins will lead to new and more reliable therapies ....Pterygia, one of the most common ocular complaints in Australia and worldwide, are thought to originate from overexposure to UV light. We propose that UV-irradiation stimulate certain cells in the eye to produce cytokines, growth factors and enzymes which degrade scaffold proteins such as collagens. These enzymes may play a key role in the progressive and invasive nature of pterygia. Dissecting the mechanism(s) by which UV light induces these proteins will lead to new and more reliable therapies for the treatment of pterygia.Read moreRead less
INTRARETINAL OXYGEN CONSUMPTION AND THE PREVENTION OF HYPOXIA IN RETINAL ISCHEMIA
Funder
National Health and Medical Research Council
Funding Amount
$164,444.00
Summary
Adequate oxygen supply to the retina is critical for normal visual function. The oxygen is normally supplied by the blood flowing in the two circulations that support the retina. These are the choroidal circulation, lying behind the retina, and the retinal circulation, which supports the front half of the retina. The retinal circulation is particularly vulnerable to vascular disease and insufficient blood flow (ischemia). Vascular changes are involved in a wide range of retinal diseases which ar ....Adequate oxygen supply to the retina is critical for normal visual function. The oxygen is normally supplied by the blood flowing in the two circulations that support the retina. These are the choroidal circulation, lying behind the retina, and the retinal circulation, which supports the front half of the retina. The retinal circulation is particularly vulnerable to vascular disease and insufficient blood flow (ischemia). Vascular changes are involved in a wide range of retinal diseases which are currently responsible for the majority of new blindness in our community. The choroidal circulation is relatively robust, and offers a potential avenue for increasing oxygen delivery to the retina in the clinical management of ischemic retinal diseases. The feasibility of such an approach is strongly dependent on the oxygen requirements of the retina, and how this is influenced by retinal ischemia. We plan to find out how much oxygen is consumed by the many different layers within the retina under normal conditions and then determine how this changes under ischemic conditions. We will then see if we can supply enough oxygen from the choroid by a combination of raising the oxygen content of the blood, increasing choroidal blood flow, and reducing the amount of oxygen used by the outer half of the retina. Our experiments will be done in laboratory rats, but the same principles are readily transferable to humans if they prove to be beneficial in protecting the retina from ischemic damage. Our study will also quantify the relationship between oxygen levels in the blood stream, and those in the different layers of the retina. This information may prove valuable in the treatment and the prevention of other retinal diseases where the manipulation of the intraretinal oxygen environment is an exciting new avenue of research.Read moreRead less
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