Australian stem cell research reveals detailed genetic roadmap of glaucoma

Professor Alice Pébay,  Anatomy and Physiology,  co-authors world-first research that used stem cell modelling to develop a detailed genetic roadmap of the leading cause of irreversible blindness.

The work, one of the largest and most detailed stem cell modelling studies reported for any disease, is published  in Cell Genomics on 8 June.

By comparing stem cell models of the retinal ganglion cells of people with Primary Open Angle Glaucoma to those with without the disease, more than 300 novel genetic features of these cells were uncovered.

The findings are the result of a national collaboration led by Professor Alice Pébay and Dr Maciej Daniszewski, of the Department of Anatomy and Physiology,  Professor Alex Hewitt of the University of Tasmania and the Centre for Eye Research Australia and Professor Joseph Powell of the Garvan Institute of Medical Research.

Professor Hewitt, who is Head of Clinical Genetics at CERA, says the study will lead to a better understanding of the mechanisms that damage retinal ganglion cells and lead to the onset of glaucoma.

This will help researchers develop new drugs to combat glaucoma, by identifying potential new areas to target to stall or reverse vision loss caused by the disease.

Healthy retinal ganglion cells – which transmit visual information from the eye to the brain via the optic nerve – are essential for vision. In glaucoma, the gradual damage and death of these cells leads to a progressive, irreversible decline in sight.

“Glaucoma is often an inherited condition and comparing diseased retinal ganglion cells with healthy one is an effective way to increase our understanding of the mechanisms that contribute to vision loss,’’ says Professor Hewitt.

“But until recently that’s been impossible because you cannot obtain or profile retinal ganglion cells from living donors without an invasive procedure,’’ says Professor Pébay, whose team lead the stem cell aspects of this work. To overcome this challenge, the scientists used Nobel Prized-winning induced pluripotent stem cell (iPSC) technology to ‘reprogram’ skin cells provided by donors into a stem cells that were then turned into a retinal ganglion cell in the lab.

They then mapped the individual genetic expression of almost a quarter of a million cells to identify features that could impact on the way genes are expressed in the cell, impacting its function, and potentially contributing to vision loss.

The researchers identified 312 unique genetic features in the retinal ganglion cell models that warrant further investigation.

“The sequencing identifies which genes are turned on in a cell, their level of activation and where they are turned on and off – like a road network with traffic lights,’’ says Professor Powell, whose team lead the analysis of world leading dataset.

“This research gives us a genetic roadmap of glaucoma and identifies 312 sites in the genome where these lights are blinking.’’

“Understanding which of these traffic lights should be turned off or on will be the next step in developing new therapies to prevent glaucoma.’’

Professor Hewitt, an ophthalmologist, says the research provides hundreds of new targets for researchers developing new drugs to treat glaucoma which is predicted to affect more than 80 million people globally by 2040.

“Current therapies are limited to slowing vision loss by reducing pressure in the eye – but they do not work for all patients and some people continue to lose many retinal ganglion cells and vision despite having normal eye pressure.

“The rich source of genetic information generated by this research is an important first step towards developing new treatments that go beyond lowering eye pressure, and can reverse damage and vision loss.’’

The research was the result of an extensive national collaboration including researchers from the University of Melbourne, Centre for Eye Research Australia, QIMR Berghofer Medical Research Institute, St Vincent’s Institute of Medical Research, St Vincent’s Hospital, Flinders University, Lion’s Eye Institute, Macquarie University, University of Tasmania and University of New South Wales.


National Health and Medical Research Council, Australian Research Council, the Joan and Peter Clemenger Foundation, the Goodridge Foundation, the Ophthalmic Research Institute of Australia, the Bright Focus Foundation, Philip Neal bequest, Stem Cells Australia, University of Melbourne. CERA receives Operational Infrastructure Support from the Victorian Government.