Sponge-like Silicon Holds New Potential for Drug Delivery
First Published: Enews June 2011
Nanotechnology research at Flinders University is opening the doors to a miniscule means of delivering drugs to directly treat blinding eye conditions and other diseases.
The research, which features a form of silicon known as porous silicon, is being led by Professor Nico Voelcker from the Faculty of Science and Engineering, who has been studying the element for more than a decade.
Porous silicon has a huge surface area similar to a sponge - just one gram can have a surface area of 1000 square metres, more than the area of a football field.
Professor Voelcker and his team hope to capitalise on this incredible surface area by attaching proven therapeutic molecules to the silicon's surface, and then inject it directly into disease sites.
"The silicon will then degrade into silicic acid which is biodegradable and is non-toxic, and is a trace element already found in human bodies," Professor Voelcker said.
Professor Voelcker is working with Professor Keryn Williams from the Department of Opthalmology to use these porous silicon molecules in conjunction with therapeutic antibodies and stem cells to prevent a patient from having to have frequent uncomfortable injections to treat eye diseases.
"We hope that by injecting these porous silicon nanoparticles into the eye, which take a long time to degrade, we will be able to release these drugs over a much longer period of time," Professor Voelcker said. "We hope to be able to halve the number of injections required by a patient, if not more."
The porous silicon also has possibilities for more effectively delivering therapeutic drugs in other diseases including cancer.
The group is currently collaborating with Associate Professor Bryone Kuss from the Department of Haematology and Genetic Pathology to explore its applications in the treatment of brain tumours.
Professor Voelcker said the material is also showing promise as a potential disease sensor.
"The silicon changes colour depending on which antibody or molecule is loaded on to it," he said.
"We have been able to show that it changes colour in the presence of autoimmune antibodies and other disease proteins."
World First Glaucoma Gene Discovery
First Published: Flinders University Marketing and Communications - May 2011
An Australian research team led by Flinders University researchers has discovered two new genes that could open the way to new treatments for blinding glaucoma.
Their findings are published online this week in the prestigious international science journal, Nature Genetics.
The study established that 18 per cent of the population carry risk variants at these two genes, making them up to three times more likely to develop severe glaucoma than those that don’t.
Other unknown factors also influence the overall risk for an individual.
The team, headed by Associate Professor Jamie Craig and Research Fellow Dr Kathryn Burdon from the Department of Ophthalmology at Flinders University, involved groups from five other Australian universities on the ground-breaking survey of 4500 patients from every state in Australia and New Zealand.
“Although open angle glaucoma is the most common form of the disease, it is poorly understood and difficult to diagnose in its early stages,” Associate Professor Craig said.
“Many cases still remain undiagnosed until irreversible loss of vision has occurred,” he said.
“Our discovery will help replace routine monitoring and hit-and-miss treatment for glaucoma, by identifying patients at the highest risk of going blind. It opens the pathway to developing completely new ways of treating patients that could delay disease progression and prevent blindness.”
Glaucoma is the collective name for eye diseases causing irreversible loss of peripheral vision, often associated with too much pressure developing inside the eyeball. It is the leading cause of irreversible blindness worldwide, affecting an estimated 300,000 people in Australia, of which half are currently undiagnosed.
“This study is the culmination of five years’ work. Before anyone else in the world, our South Australian team achieved these outstanding results,” Associate Professor Craig said.
Dr Burdon said that as part of its ongoing research, the team will examine how these genes relate to other biological measures that are relevant to glaucoma.
“By combining genetics with a better understanding of factors such as the pressure in the eye and how the optic nerve looks, we may be able to develop earlier diagnostics for glaucoma,” Dr Burdon said.
An Australasian First For Glaucoma Screening
First Published: Investigator - July 2009
Updated: World First Glaucoma Gene Discovery
Flinders Medical Centre (FMC) researchers have established Australasia’s largest registry of advanced glaucoma patients to find ways to identify those at high risk of developing the degenerative eye disease.
Glaucoma, a disease which causes gradual blindness because of high eye pressures, affects more than 300,000 Australians, but as many as half do not know they have it until irreversible vision loss has occurred.
About three percent of glaucoma cases are explained by inherited errors in a particular gene called myocilin. These cases characteristically have very high eye pressures which develop at a younger age than non-genetic glaucoma, causing challenges for the early identification of the disease.
Ophthalmologist Associate Professor Jamie Craig and his team of researchers at FMC have established the Australian and New Zealand Registry of Advanced Glaucoma (ANZRAG) in the hope of developing genetic screening tools for people who are most at risk of glaucoma blindness, so that they can be diagnosed and treated before they start losing vision.
The team will also study the DNA of advanced glaucoma patients to identify new genes linked to glaucoma and to gain a better understanding of other factors which contribute to the disease.
ANZRAG was established at Flinders in 2007 and the registry currently has 642 samples from people with advanced glaucoma from all over Australasia.
“We try to recruit as broadly as possible. Ophthalmologists in other states and New Zealand send details of patients with very severe glaucoma, and we then work with them to obtain a blood sample,” Associate Professor Craig said.
Samples are screened to see how many have the known errors in the gene myocilin which can cause severe glaucoma. If patients are found to have the genetic mutation, information and gene screening is then offered to their families.
Family members found to be carrying the myocilin changes can then be monitored and put on preventative treatments before vision loss occurs.
ANZRAG is the only organisation in Australia offering this clinical gene testing for patients with advanced glaucoma.
To obtain more information please speak with your Ophthalmologist or telephone ANZRAG on 08 8404 2035.
A Clearer Vision Of Pseudoexfoliation Syndrome
First Published: Investigator - January 2009
Flinders researchers have set pseudoexfoliation syndrome in their sights in the hope of better understanding this eye condition which is a major risk factor for developing glaucoma.
Pseudoexfoliation syndrome is an ageing disease characterised by abnormal deposits forming on the lens in the eye. It can develop into glaucoma if the deposits block the eye’s drainage pathways, leading to loss of vision or blindness.
Ophthalmologist Assoc Prof Jamie Craig, and researchers Drs Kathryn Burdon and Shiwani Sharma are using cutting edge techniques to identify the materials deposited on the lens and determine why they form.
By comparing samples taken during cataract surgery, Dr Sharma is working with the Flinders Proteomics Facility to identify proteins present in the pseudoexfoliation eye deposits which are not present in patients who do not have the syndrome.
“We have identified new proteins in pseudoexfoliation deposits which were previously not known to be present. These proteins may explain why the material is depositing,” Dr Sharma said.
The researchers are collaborating with the School of Chemistry to use an atomic-force microscope to see how these new proteins arrange themselves on the eye lens in the hope of better understanding how they form.
They are also using genomics to add further pieces to the puzzle.
It is known that a variant of the LOXL 1 gene plays a role in the formation of the protein deposits on the lens. However, not everyone who has this variant will develop pseudoexfoliation syndrome.
“We think there are a number of other genes not yet identified that contribute to the disease,” Assoc Professor Jamie Craig said.
“We also have some ideas about other factors such as ultraviolet light exposure that may increase the risk of this condition in people with the genetic predisposition.”
The researchers are conducting a genome wide scan of 250 patients who have pseudoexfoliation syndrome in the hope of identifying gene variations which are over or less represented in patients with the disease.
“The information found by these techniques will all come together and complement each other. It is incredible how far technology has come. Three years ago we would not have had a hope of understanding this disease at all.” Assoc Prof Craig said.
The Eyes Have It
First Published: Investigator - December 2008
The visual development of premature babies can be improved by enriching their diets with omega-3 oil, a medical scientist from the Child Nutrition Research Centre at Flinders Medical Centre has found.
Dr Lisa Smithers’ research work has seen her named Young Investigator of the Year for 2008.
More than 140 babies born at less than 33 weeks’ gestation took part in the trial, which involved them receiving milk rich in the omega-3 oil DHA, or the usual levels of DHA in milk.
Mothers who chose to breastfeed their infants ingested tuna oil capsules to increase human milk DHA.
Researchers then tested their visual development using a procedure devised by Lisa. Babies’ brain waves were monitored using sensors as they watched a television monitor with a series of decreasing striped patterns.
The test was carried out at two and four months of age, when babies’ visual systems are in a period of rapid development.
‘We know that DHA, an omega fat, is rich in the retina,’ Lisa said. She said DHA played an important role in converting light signals to electrical signals and then to the brain.
‘During pregnancy the developing baby gets DHA from their mothers, so babies born prematurely can miss out on this important omega fat.’
Lisa said babies in the study were provided with a level of omega fats equivalent to the amount they would have received naturally from their mothers had they been born at term.
‘We found that those babies fed DHA-rich milk had better visual development than those babies who were not,’ Lisa said.
While no differences in vision were found at two months of age, by four months babies who received the omega-3 supplements were able to see a finer pattern than the control group.
‘They were able to able to see a smaller striped pattern than the control group of babies.’
Lisa said she hoped her research findings would be used towards developing clinical guidelines in the future.
Researchers Tackle Diabetes Riddle
First Published: Investigator - July 2008
Why do some people with diabetes develop diabetic-related eye disease over others?
It may all be in the genes, according to new research at Flinders Medical Centre.
Researchers have long been confounded as to why some people with well-controlled diabetes go on to develop sight-threatening diabetic retinopathy, while others with out-of-control diabetes do not.
Clinical PhD student Dr Sue Abhary, based in the Department of Ophthalmology at Flinders Medical Centre, is trying to find out why.
‘Diabetic retinopathy is one of the complications of diabetes and while most people with diabetes will go on to develop some sign of the eye disease, in many the changes aren’t sight threatening. Some may not even notice any changes in their eye sight.’
But for some people who reach the extreme end of the scale, she said diabetic retinopathy could result in blindness.
Sue said three factors affect the development and progression of diabetic retinopathy:
- How long the person has had diabetes
- Poor sugar control
- Untreated blood pressure.
However interestingly, some people who have all these risk factors don’t develop any signs of diabetic retinopathy and vice versa.
Flinders researchers believe the answers could be found in the genes, and have begun a research project testing the DNA of patients with diabetes.
‘We think that there is a genetic component, and what we’re trying to ascertain is what gene can make one person go blind over another, and vice versa,’ Sue said.
‘She said preliminary results on 570 patients were indicating that genetics could indeed play a role.
‘While it’s still very early days, we’ve found that there is a variant of a gene in some patients that may protect them from developing diabetic retinopathy – regardless of whether their diabetes is well controlled or not.’
She said the gene called vascular endothelial growth factor (VEGF) is involved in new blood vessel formation and leakiness.
Boost For Child Health Research
First Published: Investigator - February 2008
Researchers at Flinders Medical Centre will use the first machine of its kind in South Australia to diagnose and treat childhood diseases such as asthma and eye disease.
The $500,000 instrument is known as a Linear Ion Trap mass spectrometer and is the only one of its kind in South Australia. It is used in the study of proteins.
The mass spectrometer works by identifying proteins that are involved in the formation of disease. Once identified, these proteins are used to diagnose diseases or they are targeted in the treatment of a disease.
Researchers separate individual proteins and digest them with an enzyme to produce smaller fragments known as peptides. The mixture of peptides is then separated and analysed by the mass spectrometer.
The mass spectrometer fragments the peptides and measures the mass of these fragments. The data acquired by the mass spectrometer can be searched against large databases of proteins to identify the protein and the unknown disease.
Head of the Flinders Proteomic Facility Dr Tim Chataway said the mass spectrometer is a major addition to proteomic research at Flinders.
The mass spectrometer was funded through a $300,000 grant from Variety the Children’s Charity, the Child Health Research Institute and the FMC Foundation.
Understanding Congenital Cataract Formation
First Published: Investigator - April 2007
Updated: July 2011
Researchers at Flinders discovered a gene, which when mutated, is responsible for the formation of cataracts in Nance-Horan Syndrome (NHS) and is now providing insights into the development of some congenital cataracts.
Nance-Horan Syndrome is a rare genetic condition largely affecting infant males. Along with dental defects, cranio-facial abnormalities and the probability of mental retardation, babies with NHS develop severe cataracts at birth, usually within both eyes and invasive surgery must be undertaken urgently to prevent blindness. The gene has been found to have a role in the development of the brain and teeth and is important in the development of the lens of the eye.
Dr Shiwani Sharma, Senior Research Officer in the Department of Ophthalmology, investigated this gene in the hope it could hold clues to create a better understanding of congenital cataract formation.
Cataracts are the leading cause of blindness around the world. They form when the lens of the eye develops opacity, and usually results in severe vision impairment. If not caught early enough the development of full blindness is a strong possibility.
One in every 10,000 children around the world develop congenital cataracts caused by inheriting a mutated gene or the mother getting a viral infection during pregnancy. Currently the only treatment for cataracts is invasive surgery.
“Knowledge of the genetic and molecular causes of congenital cataract will help us understand cataract formation with the ultimate aim of providing better diagnosis and timely treatments for such disorders,” said Dr Sharma.
Dr Sharma said that while studies in the NHS gene are not being actively pursued, the research has provided leads to the understanding of development of some congenital cataracts.
"Our team have now found another gene, called EphA2, that causes congenital cataracts and is involved in age-related cataracts as well.
"We are currently conducting further studies on this gene in both types of cataracts."
Tackling Corneal Transplant Rejection
First Published: Investigator - April 2006
A new research project currently underway at Flinders Medical Centre is focused on reducing the risk of corneal transplant rejection. Transplant rejection occurs when the immune system attacks the transplanted organ or tissue because it is foreign to the body.
Each year in Australia up to 1,500 corneal transplants are performed to correct visual impairment, around 50 of these take place at Flinders Medical Centre. The cornea is the curved, transparent layer that covers the front part of the eye and protects its inner structures. When the cornea becomes opaque due to either trauma or disease, light is unable to reach the retina at the back of the eye which significantly reduces sight.
The surgery involves removing the damaged part of the cornea and replacing it with a piece of normal cornea taken from the eye of a donor. The Eye Bank of South Australia, situated at Flinders Medical Centre, is responsible for collecting the donated corneas which are then stored for up to four days. It is this four day window of opportunity that is of particular interest to the research team Associate Professor Keryn Williams, Professor Doug Coster and Dr Helen Brereton are involved in.
While it is unusual to see early rejection with corneal grafts, as opposed to major organ transplants, this can still occur over a much longer period. The Australian Corneal Graft Register indicates that the success rate in terms of restoration of vision is less than 60% after 10 years – that is six in every 10 patients will retain good vision for up to 10 years.
Rejection is the major cause of the failure for the other 40% of recipients. The researchers want to develop a simple intervention directed at the donor cornea before it is transplanted to minimise this risk of rejection.
“A major part of the research is identifying the right protein that will help stop rejection, currently we have identified a protein that works in two thirds of our experimental cases,” says Associate Professor Williams.
Using a gene therapy approach, they will insert a gene which has been programmed to produce an identified anti-rejection protein into the donor cornea. This gene will cause the cornea to express more of the desired protein helping to minimise the risk of rejection.
Professor Williams acknowledges that the research is in the very early stages but their aim to reduce the number of recipients who experience rejection will be an extremely worthwhile outcome.
Eye Drops To Help Save Eye Sight
First Published: Investigator - July 2003
A simple eye drop could be the answer to prevent abnormal blood vessels that cause eye disease.
Major research currently being conducted at Flinders by PhD student Peter van Wijngaarden, using proteins as a source of medication in the form of eye drops, could herald a new technique to prevent development of abnormal blood vessels that can lead to eye disease.
Dr van Wijngaarden’s aim is to target the growth factors responsible for the formation of these abnormal blood vessels. The technique will use antibodies that target specific molecules within the eye by binding to the chemicals that are responsible for the abnormal vessel growth and in turn stopping their effect and preventing new vessels from forming.
"To date, the technology has been limited by the fact that the delivery of these therapies has required injections into the eye which is very confronting and can cause a lot of damage. Developing an eye drop to prevent abnormal blood vessels in the eye is very appealing,” said Dr Wijngaarden.
The discovery occurred in 2001, when Peter’s supervisor Keryn Willams along with Michael Thiel realised that an antibody can make its way into the back of the eye when used as an eye drop.
Dr Wijngaarden. envisages this therapy will initially be used on diabetes patients who may have early signs of eye disease and also for those patients with more advanced disease, to prevent further progression and visual loss as a result. In the future, it is hopeful that this technique will be used for a subset of patients with macular degeneration.
Diabetes and macular degeneration (the degeneration of the portion of the retina responsible for detailed vision) are the two leading causes of blindness in the developed world. Dr van Wijngaarden believes that such therapies are likely to have a major impact, but cautions that it may be many years before it is available to patients.