Macquarie University ophthalmology researchers have discovered a link between the protein neuroserpin and glaucoma and developed a technique for a gene therapy that could help treat the world’s leading cause of irreversible blindness.
Professor Stuart Graham, head of ophthalmology and vision science at Macquarie Medical School, is leading a team that is investigating the role of neuroserpin in the disease.
Glaucoma is the world’s leading cause of irreversible blindness, affecting about 300,000 Australians and more than 70 million people globally.
Graham, together with vision neurobiologist Associate Professor Vivek Gupta and vision scientist Dr Nitin Chitranshi, also at Macquarie Medical School, said 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,” Gupta said.
“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,” he said.
The researchers said there is optimism gene therapy will be a valuable addition to other treatments that make eye nerves more resistant to the mechanisms that cause glaucoma.
The team has discovered that when neuroserpin oxidises – oxidation being a common cause of molecular breakdown in nature, such as iron rusting or a cut apple turning brown – 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.
Chitranshi said in their 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,” he said.
“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 said 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 said.
“But we still have a lot of work to do before we can translate this to human studies.”
This study was funded by a National Health and Medical Research Council Ideas Grant.
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