A+ A-

Study & Careers

Affiliated with the University of MelbourneUniversity of Melbourne Logo

Evidence-Based Practice in the Management of Glaucoma Suspects

Research Area: Glaucoma, Evidence Synthesis, Clinical Practice

Supervisors: Dr Zhichao Wu (wu.z@unimelb.edu.au), Dr Laura Downie (ldownie@unimelb.edu.au)

Suitable For: PhD or MPhil

Rationale: Glaucoma is a leading cause of irreversible vision loss in Australia and worldwide, with half of the those with this condition being undiagnosed. Approximately one in ten Australians over 50 years old would fit the criteria for being a glaucoma suspect, but there is limited evidence about how to identify those at high-risk of developing glaucoma and who prophylactic treatment is warranted for. The main evidence guiding the management of glaucoma suspects is based on two trials for those with ocular hypertension (i.e. raised intraocular pressure) from over 20 years ago, and individuals with ocular hypertension make up less than a half of those with suspected glaucoma.

This project will thus involve synthesising and critically appraising the evidence currently available, as well as obtaining prospective data on current practice patterns on the management of glaucoma suspects, so as to provide evidence-based guidance and identify key knowledge gaps that requires robust, prospective studies to address.

Satellite imaging technology to detect the early signs of Glaucoma and Alzheimer’s Disease in the Retina

Research Area:Diabetic Retinopathy and Neuroglial Interactions Unit
Supervisor: Dr Peter van Wijngaarden
Email: peterv@unimelb.edu.au

We aim to be the first group in the world to bring hyperspectral imaging, based on NASA satellite technology, to the clinic to improve the care of Australians with glaucoma and Alzheimer’s disease. There are no screening tests for the earliest stages of the diseases. 400,000 Australians live with dementia and most have Alzheimer’s disease. Abnormal proteins accumulate in the brain and retina for 10-20 years before memory impairment, providing an opportunity for early detection and treatment. There are no screening tests for the earliest stages of the disease. Similarly, glaucoma is a leading cause of vision loss affecting 300,000 Australians. Early treatment can save vision, but late diagnosis is typical. The deposition of abnormal proteins in the retina in Alzheimer’s disease and structural changes in the nerve cells affected by glaucoma scatter light in characteristic ways which we can detect with our camera during the early stages of disease. Students with an interest in mathematics and computing are welcome to apply.

Bioenergetics in the Optic Nerve

Research Area:Diabetic Retinopathy and Neuroglial Interactions Unit
Supervisor: Dr Peter van Wijngaarden
Email: peterv@unimelb.edu.au

Glaucoma is a neurodegenerative disease, strongly associated with ageing and high intraocular pressure. Recent work has suggested that metabolism and energy supply in the retinal ganglion cells may also play a critical role. In the optic nerve, energy is supplied to neurons by oligodendrocytes (through the intercellular transport of lactate). While it is known that this relationship is important for nerve health, little is known about how it changes with age or during periods of stress.

This project will determine how optic nerve energy supply changes with age and high intraocular pressure. Additionally, using pharmacological and genetic manipulations to block lactate transport in animal models of glaucoma, this project will investigate if perturbation of energy supply predisposes the optic nerve to damage.

A global approach to combat keratoconus

Research Area: Ocular Genetics
Supervisors: Prof Paul Baird, Dr Srujana Sahebjada, A/Prof Mark Daniel
Email: Srujana.sahebjada@unimelb.edu.au

Keratoconus is a common condition that affects the cornea and despite its increasing prevalence, the cause of keratoconus is largely unknown. Research centres across the world have individually collected cohorts of patients with keratoconus to better understand the underlying molecular causes, clinical characteristics and treatment options of keratoconus in order to develop strategies that can halt the disease progression. However, these approaches have so far been piecemeal. So, we established a global collaborative keratoconus initiative, the Keratoconus International Consortium (KIC). KIC is an overarching vehicle that consolidates all research within the field and generates collaborative opportunities to address key issues faced by keratoconus patients. The project involves collection of large datasets from the consortium, database maintenance and an exciting opportunity to conduct big data analysis and manuscript writing.

Students with backgrounds in computer science and database software’s, statistics or optometry and visual science are welcome to apply.

Neuroprotective electrical stimulation in retinal and optic nerve disease

Research Area: Neuroprotection, Macular Research Unit
Supervisors: A/Prof Chi Luu and Dr Carla Abbott
Tel: +613 9929 8172 / (03) 9929 8380
Email: cluu@unimelb.edu.au / c.abbott@unimelb.edu.au

Suitable for: Masters/PhD

Glaucoma is an eye condition associated with a progressive loss of the retinal ganglion cells and their axons (optic nerve fibres) at the back of the eye. Current treatments for glaucoma are not fully effective in preventing ongoing vision loss in many patients, so new or adjunct therapies are required. Retinitis pigmentosa is a genetically inherited disease, causing loss of the photoreceptors (cells that detect light) in the retina. Currently, there are no treatment options available.

There is increasing evidence that chronic stimulation of the retina with a low level electrical current can protect against the retinal neurons from dying (so-called neuroprotective stimulation). This neuroprotective effect is thought to be through mechanisms of electrical stimulation induced activation of the survival system, which triggers a cascade of events including upregulation of several endogenous neurotrophic factors and anti-apoptotic genes, and downregulation of pro-apoptotic genes and inflammatory cytokines.

The project aim is to investigate whether chronic electrical stimulation prevents loss of retinal neurons in preclinical models of glaucoma and retinitis pigmentosa. Skills acquired from this project include microsurgery, electrophysiology, retinal imaging, neural stimulation, retinal histology, immunohistochemistry, statistical analysis and writing scientific papers.

Enabling Treatment Trials of Atrophic Age-Related Macular Degeneration

Research Area: Age-Related Macular Degeneration, Clinical Biomarkers
Primary Supervisor: Dr Zhichao Wu
Tel: +613 9929 8369 / Email: wu.z@unimelb.edu.au

Suitable for: PhD

Although treatments currently exist for the acute, neovascular complications of age-related macular degeneration (AMD), individuals that develop atrophic complications currently face an inevitable future of progressive central vision loss since no effective treatments are available to prevent or slow the unrelenting degeneration of the retina. Although many clinical trials are now underway for atrophic AMD, a significant barrier to their success is the lack of precise clinical measures to determine their efficacy. Furthermore, trials evaluating novel treatments for the atrophic complications of AMD may be evaluated in eyes where the disease is already too advanced.

This project will involve developing novel visual function techniques tailored for the specific stages of the atrophic disease process, especially for the early stages of the atrophic process where no outcome measures have yet been established. This will provide the necessary tools needed as a catalyst for the discovery of interventions for the debilitating complications of atrophic AMD.

Taking the “Guesswork” Out of Glaucoma Clinical Management with Novel Imaging

Research Area: Glaucoma, Clinical Biomarkers
Primary Supervisor: Dr Zhichao Wu
Tel: +613 9929 8369 / Email: wu.z@unimelb.edu.au

Suitable for: PhD

The clinical management of glaucoma seeks to prevent patients from experiencing visual disability from the progressive degeneration of retinal ganglion cells. This task is especially difficult by the lack of effective methods to detect and characterise disease progression accurately and meaningfully. Current clinical tests are currently so variable that clinicians are often left with a great deal of “guesswork” in the clinical management of glaucoma. Optical coherence tomography is a modern clinical imaging technique that could accurately detect disease progression and predict long-term outcomes, given its ability to non-invasively visualise the retina three-dimensionally at near-cellular resolution. This powerful technology could be exploited to transform the clinical management of glaucoma patients.

This project will involve development of this imaging technique and analytical methods and understanding its relation to patient-reported measures of visual disability to understand the clinical relevance of its results.

Repair of the cornea to restore vision

Research Unit: Corneal Research
Primary supervisor: Dr Mark Daniell / Professor Greg Dusting
Tel: +613 99298078 / Email: g.dusting@unimelb.edu.au

Severe burns and corneal disease leads to vascularization and ulceration of the corneal surface, which is currently treated by corneal transplants and lifelong anti-rejection drugs. Many countries in the world do not have sufficient donors to meet the increasing demand for this procedure. At CERA we work closely with chemical engineers and veterinary scientists at the University of Melbourne to develop engineered constructs to replace the damaged corneal endothelium.

The current project is to develop a source of corneal endothelium from human induced pluripotent stem cells (iPS cells), and grow these on patented hydrogel films to replace damaged endothelium. Alternatively, the reprogramming of appropriate patient cells direct to corneal endothelium will be explored. Mechanisms of adhesion and proliferation of these cells will be examined, and preclinical transplantation studies will be carried out in sheep in the veterinary facility. This project would be suitable for biomedical science students with an interest in cell biology, pharmacology or ophthalmology to work towards clinical application of this novel technique with an ophthalmologist, stem cell scientist, veterinary scientists and other cell biologists.


Identification of protective pathways in mitochondrial disease: what protects retinal cells from Leber’s hereditary optic neuropathy?

Research Area: Genetics, stem cell biology, bioinformatics
Primary Supervisor: Dr Isabel Lopez Sanchez
Tel: +613 8532 1972 / Email: isabel.lopez@unimelb.edu.au

Project suitable for: Honors, Masters, Medical Student (6-month commitment required)

Essential qualifications: BSc or BSc (Hons)

Start date: first or second semester 2018

Project outline: Leber’s hereditary optic neuropathy (LHON) is an inherited mitochondrial disease that can cause sudden onset of blindness predominantly in young men. Amongst people who carry a LHON mitochondrial DNA mutation, some go blind (LHON affected patients) whilst others maintain good vision throughout life (LHON unaffected carriers), indicating that blindness can be prevented. However, no one has investigated the protective factors that prevent vision loss naturally in LHON unaffected carriers.

In this project, we will combine our mitochondrial and stem cell expertise to generate retinal cells using skin cells from LHON affected patients and LHON unaffected carriers. We will then use the latest genomic sequencing technology to identify protective pathways in cells from unaffected LHON carriers.

This project involves the use of a range of techniques in cell biology (cell culture), stem cell biology (cell reprogramming, iPSC generation and differentiation), biochemistry (immunostaining, mitochondrial function assays), molecular biology (DNA extraction, PCR) and bioinformatics.

Development of regenerative therapy for photoreceptor losses using cell reprogramming technology

Research Unit: Cellular Reprogramming
Primary supervisor: Dr Raymond Wong
Tel: +613 99298054 / Email: wongcb@unimelb.edu.au

Photoreceptors are light-sensing cells that form the basis of our vision by converting light into electrical signals that can be decoded by the brain.  the loss of photoreceptors is a key hallmark of many blinding diseases, such as retinitis pigmentosa, age-related macular degeneration, and diabetic retinopathy.  These diseases affect millions of patients and cause a significant socis-economic burden on our healthcare system. Currently, there are no effective means to cure blindness once photoreceptors are lost.  We must therefore find a new approach to help restore vision to these patients.  Regenerative therapy to replace photoreceptors has the very real prospect of helping patients to restore vision.

Cell reprogramming could be the key to this critical issue.  This innovative technology relies on converting one cell type into another by rewriting the transcriptome to alter the cell’s identity.  One of the most famous examples is the Nobel prize-winning discovery of induced pluripotent stem (iPS) cells, in which the altered expression of four transcription factors converted adult fibroblasts into stem cells.  Beyond iPS cells, direct reprogramming is now possible by converting one somatic cell type directly to another, such as fibroblasts to neurons, without passing through an intermediate stem cell state.  this project aims to develop cell reprogramming technology to generate new photoreceptors, providing novel regenerative therapy approach to treat photoreceptor loss.  Techniques involved in this project include cell reprogramming, CRISPR/Cas9, transcriptomic analysis, molecular cloning, fluorescent micrscopy and virus generation.

Using pluripotent stem cells to model AMD

Research Unit: Neuroregeneration
Primary Supervisor: Dr Alice Pébay
Tel: +613 9929 8165 / Email: apebay@unimelb.edu.au

Age-related macular degeneration (AMD) is the leading cause of blindness in the developed world. Virtually nothing is known about how or why retinal cells die in AMD; however, genetic background is a significant risk factor. Our research uses stem cells from patients with eye diseases to better understand the underlying cause of diseases. In this project, we will reprogram skin and hair cells from these patients with specific genetic risk associated with AMD into induced pluripotent stem cells, and then drive the stem cells to become retinal pigmented epithelial cells to create an in vitro model in which to study AMD pathogenesis. By examining how these retinal cells die, we expect to find ways to block this process, which is an important step towards developing therapies.