We use established and novel approaches to patient assessment and treatment to combat retinal blindness. Our main areas of research are
The work of our group focuses on laboratory and clinical research projects aimed at addressing major causes of irreversible sight loss.
Inherited retinal diseases (IRDs) affect up to 1 in 3,000 individuals and are now the commonest cause of vision loss in people of working age. One of the problems with developing treatments for IRDs is their diversity: more than 300 genes have been implicated. Furthermore, some approaches (e.g. gene replacement) may prove unsuitable for patients with advanced disease. Optogenetics is an approach which aims to circumvent these problems.
The final common pathway to sight loss in IRD is loss of the primary neurons of the retina (the photoreceptors). Optogenetics is a technique which renders the secondary and tertiary neurons light sensitive, thereby restoring function by converting them into novel photoreceptors. This is achieved through the introduction of genetic sequences which code light sensitive proteins, or opsins. We are investigating the ability of bReaCheES, a novel modified microbial opsin, to restore vision in models of advanced retinal degeneration.
The optogenetics program is supported by the Foundation Fighting Blindness and the Sydney Medical School Foundation.
Retinal explant project
We have developed protocols for harvesting and storing living donor human retinal explants collected during emergency surgery for retinal detachment repair. These explants have been used for proof-of-concept testing of gene therapy vectors. This model is also being utilised as a potential source of retinal progenitor cells.
This work is supported by the Foundation Fighting Blindness.
We use psychophysical techniques, including selective perimetry, threshold versus intensity testing, colour vision assessment and dark adaptation to explore clinical phenotypes and to design appropriate tests for characterising and monitoring function in patients with retinal disease.
We also seek to explain clinical observations through hypothesis driven psychophysical testing. Results are correlated with advanced imaging modalities such as optical coherence tomography. Ultimately, we hope to predict function based upon structure.
This work is supported by the Foundation Fighting Blindness and the Global Ophthalmology Awards program.
New retinal therapies, such as gene therapy and stem cell therapy, mandate new surgical approaches. One such technique is subretinal injection. We are comparing two different methods of subretinal injection – so-called one-step injection in which the therapeutic solution is used to simultaneously define the surgical plane and two-step injection, in which the surgical plane is first defined by subretinal injection of balanced salt solution. This trial is currently recruiting and is registered with the Australian and New Zealand Clinical Trials Registry.
The subretinal injection trial is supported by the Foundation Fighting Blindness.
ONL1204 is a first in class inhibitor of Fragment Apoptosis Stimulator receptor (Fas)-mediated cell death. It has demonstrated neuroprotection to multiple retinal cell types in models of ocular injury. We are the lead site for a Phase I trial of ONL1204 for macula-off retinal detachment.
The Renexus Trial is a Phase III investigation of a surgically implanted ciliary neurotrophic factor (CNTF) eluting device for patients with macular telangiectasia type II. The Macular Research Group is conducting the trial, with our group undertaking the surgical procedure. Recruitment recently closed and we are pleased to report that our site performed the largest number of implantation surgeries worldwide.