A treatment that ensures nerve cells in the eye continue to produce a vital protein that protects them from being broken down could help prevent the progression of glaucoma, researchers have found.
Discovery: Macquarie ophthalmology researchers are the first to find a link between the protein neuroserpin and glaucoma, the world’s leading cause of blindness.
Glaucoma is the world’s leading cause of irreversible blindness, affecting about 300,000 Australians and more than 70 million people globally. It is associated with gradual vison loss, initially in the periphery but then spreading centrally. The disease damages the optic nerve and the retinal ganglion cells, which are a type of neuron that carry visual information to the brain.
Glaucoma is often associated with increased pressure in the eye, and it can be detected during routine vision tests, by measuring the eye pressure or inspecting the optic nerve for damage with special scanners.
While any damage already sustained cannot be reversed, in many cases the progression of the disease can be slowed or stopped through treatment to lower the pressure.
However, many patients continue to worsen despite treatment, indicating there are other factors at play in addition to pressure.
Professor of Ophthalmology Stuart Graham from Macquarie Medical School is leading a team that is investigating the role of the protein neuroserpin in the disease.
A first
Vision Neurobiologist Associate Professor Vivek Gupta says they have found that neuroserpin, which is produced in the connectors between nerve cells, is vital in protecting retinal ganglion cells.
“Other researchers have linked changes in neuroserpin to stroke and neurodegenerative disorders like Alzheimer’s and Parkinson’s diseases, but our work is the first to relate it to glaucoma,” says Professor Gupta.
“Cells naturally break down and are recycled in the body, but when neuroserpin is absent, this process speeds up in the retina.
“Essentially, the body begins to eat away at the retinal ganglion cells and the optic nerve.”
Hope in sight: Professor Graham says but there is optimism that gene therapy will be a valuable addition to other treatments that make eye nerves more resistant to the changes that cause glaucoma.
Oxidation is a common cause of molecular breakdown in nature. Iron rusting and a cut apple turning brown are both familiar examples.
The team has discovered that when neuroserpin oxidises, it loses its protective ability, allowing accelerated cell breakdown.
They have also shown that when mice produce more neuroserpin, it has a protective effect, promoting the survival of the retinal ganglion cells and minimising glaucoma damage.
Vision Scientist Dr Nitin Chitranshi says in the latest work, detailed in an article in the latest edition of Molecular Therapy, the team has successfully manipulated a gene in mice to produce a version of neuroserpin that is resistant to oxidation.
“When we introduce this gene directly to the eye, it increases the production of neuroserpin in the retina,” says Dr Chitranshi.
“Currently, that involves injecting it into the eye, which is obviously quite confronting, but we are working on a way to introduce the gene using a synthetic virus that can be targeted to specific cells in the retina.
“The artificial virus would not have any effect on the body, but would act as a carrier for the therapy, allowing our specially developed nanoparticles to get inside the cells and tell them to produce our modified neuroserpin.
“We are also working on a way for the protein to give its instructions to produce neuroserpin only to the retinal ganglion cells and not to other neurons, so it can be perfectly targeted.”
The team is now preparing for further testing of the enhanced gene and will commence new trials shortly.
Professor Graham says glaucoma is a complex disorder involving a number of mechanisms, not all of which are well understood.
“For this reason, our gene therapy is unlikely to be a silver bullet for all glaucoma, but we have great hopes that it will become a valuable part of treatment for use in conjunction with other therapies, making the nerve cells more resistant to damage,” he says.
This study was funded by a National Health and Medical Research Council Ideas Grant.
Professor Stuart Graham is Head of Ophthalmology and Vision Science at Macquarie Medical School.
Associate Professor Vivek Gupta is a Vision Neurobiologist and an NHMRC Dementia Research Fellow. He leads the Vision Neurodegeneration Research Group at Macquarie Medical School.
Dr Nitin Chitranshi is a Vision Scientist at Macquarie Medical School.
