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
THE ROLE OF MONOCYTIC LINEAGE CELLS IN MODELS OF CORNEAL DISEASE
Funder
National Health and Medical Research Council
Funding Amount
$311,567.00
Summary
Vision relies on sharp, focused undistorted images passing through the cornea, the clear 'window' at the front of the eye. Corneal disease causes over 5 million cases of blindness worldwide. In patients who damage the delicate covering of the cornea, due to trauma or contact lens wear, there is an increased risk of infection that may lead to blindness. This project will study the ways in which immune cells in the cornea detect invasion by potential pathogens.
Genetic And Molecular Basis Of Congenital Cataracts
Funder
National Health and Medical Research Council
Funding Amount
$454,510.00
Summary
Cataracts are caused when the lens of the eye (which focuses light), loses transparency. They typically occur in older individuals, but can also occur in children, even as early as from birth. They usually result in severe vision impairment which can result in complete blindness. The only treatment is invasive surgery where the outcomes are poor, particulary in very young children. This research aims to discover the genes that cause cataract in children and to investigate how cataracts form. We ....Cataracts are caused when the lens of the eye (which focuses light), loses transparency. They typically occur in older individuals, but can also occur in children, even as early as from birth. They usually result in severe vision impairment which can result in complete blindness. The only treatment is invasive surgery where the outcomes are poor, particulary in very young children. This research aims to discover the genes that cause cataract in children and to investigate how cataracts form. We are working with several large Australian families that have severe childhood cataracts in order to identify the specific genes that cause their disease. This is achieved through an investigation of the entire genome of these families which allows us to precisely pinpoint any genetic changes. We can then look for these changes in the genes in other childhood cataract patients as well as in adults with cataracts. This information will increase our understanding of how the lens of the eye works and how cataracts can form. One gene that can cause cataracts has already been identified, this is the Nance-Horan Syndrome gene. We will investigate the role of this gene in the lens of the eye. This gene also causes other severe disabilities including mental retardation. The exact function of this gene is unknown but by determining how it works we will be able to better understand cataract formation and mental retardation, with the ultimate aim of developing better diagnosis and timely treatment for these disorders.Read moreRead less
The Roles Of Beta-catenin, APC And The Wnt/beta-catenin Pathway In Lens Development And Cataract
Funder
National Health and Medical Research Council
Funding Amount
$456,764.00
Summary
Cataract is a leading cause of blindness. Many risk factors have been identified but the basic cellular and molecular mechanisms that cause cataract are not well understood. Investigation of these mechanisms is essential to identify potential targets for future therapies to arrest or prevent cataract formation. The lens is composed of epithelial and fibre cells. Much of our research has focussed on identifying genes and cell signalling pathways that regulate formation of fibre cells from the epi ....Cataract is a leading cause of blindness. Many risk factors have been identified but the basic cellular and molecular mechanisms that cause cataract are not well understood. Investigation of these mechanisms is essential to identify potential targets for future therapies to arrest or prevent cataract formation. The lens is composed of epithelial and fibre cells. Much of our research has focussed on identifying genes and cell signalling pathways that regulate formation of fibre cells from the epithelial cells. However, considerably less is known about factors that regulate formation of the epithelium itself. As the epithelial cells are affected in some types of cataract it is vitally important to understand the mechanisms that control formation and maintenance of these cells. Our previous studies have identified a growth factor family (TGF-beta) that causes epithelial cataracts. Importantly, our recent studies have identified another growth factor signalling pathway (Wnt-beta-catenin) as being essential for the formation and maintenance of the lens epithelium. We hypothesise that this pathway is disrupted dring cataract formation. This project uses state of the art tools and techniques to investigate the role of two central molecular components of this Wnt pathway (APC and beta-catenin) in the developing lens. By genetically manipulating the activity of these proteins in the mouse lens we will investigate the roles these molecules and the Wnt signalling pathway play in lens development and whether inappropriate activity results in abnormal development or cataract. We will also be able to investigate whether modulating this pathway affects the formation of epithelial cataracts by TGFbeta. The results will provide detailed information on how these molecules regulate lens structure and function and have the potential to identify targets for preventing or ameliorating cataracts.Read moreRead less
Development And Evaluation Of Teleophthalmic Systems For Screening Of Common Blinding Eye Diseases
Funder
National Health and Medical Research Council
Funding Amount
$263,918.00
Summary
Portable ophthalmic instruments will provide digital images for storage and telemetric transmission to a disease control centre. We will be assessing and developing new portable ophthalmic imaging instruments, and validating them for common blinding eye conditions. The aim is to assess the ability of various health personal to document glaucoma, diabetic retinopathy, active trachoma, corneal scarring and cataract in rural screenings using digital imaging technology. A network of ophthalmologists ....Portable ophthalmic instruments will provide digital images for storage and telemetric transmission to a disease control centre. We will be assessing and developing new portable ophthalmic imaging instruments, and validating them for common blinding eye conditions. The aim is to assess the ability of various health personal to document glaucoma, diabetic retinopathy, active trachoma, corneal scarring and cataract in rural screenings using digital imaging technology. A network of ophthalmologists, health department personnel and aboriginal health workers in Western Australia will be involved. The project will also examine the quality of images obtained by health workers with various levels of skills and compare this with conventional photographs currently obtained by the screening network. Finally, the project will demonstrate practicality of the large scale storage of digital images of patient eyes. Preliminary evaluations have been performed on our teleophthalmology system using different portable instruments namely a handheld fundus camera, slit-lamp and indirect ophthalmoscope. We have also tested our teleophthalmology system at the Dr. Soetomo Hospital (Airlangga University) in Surabaya, Indonesia. Images captured using the handheld fundus camera were successfully transmitted to Lions Eye Institute through satellite, mobile and Internet lines. This pilot project has been sponsored by the Western Australian Department of Trade and Commerce and Telstra.Read moreRead less
Development Of A Novel Bioengineered Tissue Construct For Repairing The Eye.
Funder
National Health and Medical Research Council
Funding Amount
$335,817.00
Summary
Corneal diseases are often treated using donor tissue transplants. Nevertheless, donor tissue is unsuitable for treating the peripheral or limbal margin of the cornea. We have therefore developed a way to transplant sheets of limbal tissue (epithelium) grown in the laboratory from a patient's own cells, but this tissue lacks a foundation of connective tissue that we believe is essential for sustained healing. Thus, our aim is to develop a novel limbal transplant which contains both layers.
Therapeutic Control Of Pathological Myopia: Role Of Transforming Growth Factor-beta
Funder
National Health and Medical Research Council
Funding Amount
$312,730.00
Summary
Myopia (shortsightedness) 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. The optical consequences of myopia, namely blurred distance vision, are correctable with spectacles or contact lenses. However, a significant minority of individuals (3% of the Australian population) have excessively long eyes and high amounts of myopia. These enlarged eyes impose abnormal stresses on the s ....Myopia (shortsightedness) 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. The optical consequences of myopia, namely blurred distance vision, are correctable with spectacles or contact lenses. However, a significant minority of individuals (3% of the Australian population) have excessively long eyes and high amounts 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. Damage that occurs to the retina in these eyes is, at present, untreatable and irreversible and can result in blindness. Myopia is the 2nd leading cause of blindness amongst adults of working age. 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 a biochemically active process and not due to passive stretch. Before elongation of the eye can occur the biochemical structure of the sclera must change, a complex process involving accelerated production and breakdown of the biochemical building blocks of the sclera. Previous research in our laboratory indicates that changes in structure of the sclera are associated with reduced levels of the growth-controlling protein transforming growth factor-beta (TGF-beta). The aim of this project is to supplement TGF-beta levels in the sclera in order to reverse the loss of scleral tissue, stop the development of myopia and, therefore, prevent the development of the sight-threatening pathology associated with high myopia. In addition, we will determine the most effective way to deliver a sustained dose of TGF-beta to the sclera.Read moreRead less
Role Of Primary Cilia And PCP Proteins In Lens Development: Implications For Lens Regeneration After Cataract Surgery
Funder
National Health and Medical Research Council
Funding Amount
$413,742.00
Summary
Cataract extraction is the most common surgical procedure conducted in our hospitals today. Unfortunately, a complication of surgery is the development of a secondary cataract. This is caused by residual lens epithelial cells undergoing a wound healing response that leads to severe scarring and loss of vision. This project will identify the factors that are needed to maintain lens epithelial cells in a normal state so that they can act as stem cells that can be induced to regenerate a new lens t ....Cataract extraction is the most common surgical procedure conducted in our hospitals today. Unfortunately, a complication of surgery is the development of a secondary cataract. This is caused by residual lens epithelial cells undergoing a wound healing response that leads to severe scarring and loss of vision. This project will identify the factors that are needed to maintain lens epithelial cells in a normal state so that they can act as stem cells that can be induced to regenerate a new lens that can transmit and focus light as normal.Read moreRead less
Blue Mountains Cohort Study: Long-term (15-year) Incidence Of Eye Disease, Hearing Loss And Other Public Health Outcomes
Funder
National Health and Medical Research Council
Funding Amount
$837,919.00
Summary
The Blue Mountains Eye Study 15-year study will re-examine survivors of the 3,654 persons who participated in baseline BMES exams, to determine the long-term development and progression of sensory problems, including vision and hearing loss and eye diseases like macular degeneration, glaucoma, cataract or diabetic eye damage. The project will assess whether vascular conditions like high blood pressure, chronic medical conditions, medications, smoking, diet, blood, family and genetic factors pred ....The Blue Mountains Eye Study 15-year study will re-examine survivors of the 3,654 persons who participated in baseline BMES exams, to determine the long-term development and progression of sensory problems, including vision and hearing loss and eye diseases like macular degeneration, glaucoma, cataract or diabetic eye damage. The project will assess whether vascular conditions like high blood pressure, chronic medical conditions, medications, smoking, diet, blood, family and genetic factors predict the risk or age at onset of eye disease or hearing loss. We will assess impacts of vision and hearing loss on independence, falls, quality of life and development of memory loss and depression. This information will help to develop services, and to plan interventions to prevent and treat these conditions. Because of the exponential age-related increase in frequency of these diseases, this long follow-up will provide more disease events, and a longer interval to assess impacts from the exposures we measured when we started the BMES in 2002. It will enable us to estimate the strength of risk factors for eye disease and hearing loss with greater precision, essential to understand their evolution. Surviving participants from the original BMES will be invited to attend follow-up exams at our Katoomba clinic, or to attend mobile- nursing home exams. We will conduct similar exams to those previously to detect new or worsened eye disease or hearing loss. In 2002-4, we saw 82% of the population of 2 Blue Mountains postcodes aged 50 or older. At the 5- and 10-year exams we saw 75% of people still living. We expect the same proportion to participate this time. The BMES is one of Australia's main cohort studies with over 200 publications. It has yielded key findings on the frequency and causes of the major diseases threatening vision and hearing. Longer follow-up will greatly increase our power to detect predictors of these key age-dependent conditions.Read moreRead less