Researchers, supported by the Phenomics Australia node, the Stem Cell Disease Modelling Laboratory, have identified distinct biological features linked to a high risk of developing a severe form of age-related macular degeneration (AMD).
This story was first published on the University of Melbourne’s website.
Their findings, published in Genome Medicine, could help inform future efforts to develop more targeted treatments for people at greatest risk of developing severe macular degeneration and losing their sight.
AMD is a leading cause of vision loss and affects one in seven Australians aged over 50 and more than 196 million people worldwide. Current treatments can only slow progression once significant damage has occurred – and are only suitable for some patients.
The research team was led by the University of Melbourne, the Centre for Eye Research Australia (CERA) and the Garvan Institute of Medical Research. It investigated a form of AMD characterised by unusual deposits in the retina called reticular pseudodrusen, which are linked with a higher risk of progression to severe forms of AMD.
Researchers collected skin biopsies from more than 100 Australians with AMD, including some with reticular pseudodrusen and others without. They then used stem cell technology, supported by the Phenomics Australia node, the Stem Cell Disease Modelling Laboratory, to turn the skin cells into retinal cells in the lab and compared the two groups to see how the cells differed at the molecular level, including which genes and proteins were active.
“Our study showed that patients with reticular pseudodrusen appear to have distinct underlying biology compared to the usual form of AMD,” lead author, Professor Alice Pébay AM from the School of Biomedical Sciences and Melbourne Medical School, said.
“In particular, we see greater involvement of processes that help support cells, their structure and stability.
“The key point is that not all AMD is biologically the same, even though it can look similar clinically.”
Co-lead author, Professor Robyn Guymer AM, Deputy Director of CERA, said the study was an important step in understanding the drivers of vision loss in AMD and why particular treatments may not work for all patients.
“The study is further evidence that we need to move beyond considering AMD as a single, uniform disease to a group of related conditions that could need different treatments,” Professor Guymer said.
“The lab findings provide a great foundation for further research to develop precision therapies to prevent vision loss from all forms of AMD.”
The research was part of the Synergy High Risk AMD Project, which is a collaboration between CERA, the University of Melbourne and WEHI, funded by the National Health and Medical Research Council.
Phenomics Australia provides a national centre of expertise and service provision to deploy a more comprehensive and sophisticated range of in vitro Genome Engineering and Disease Modelling capabilities to understand the functional consequences of DNA sequence variation in the human genome for health and disease while maintaining the expertise for in vivo disease modelling and genome engineering. To meet the high demand for adaptable and scalable disease-modelling platforms for improved diagnosis, Precision Medicine for genetic disorders, and therapeutic development by both academia and the biopharmaceutical industry, Phenomics Australia offers In Vitro services through a collaborative consortium of ten laboratories and facilities across Australia, operating at ANU (ANU Centre for Therapeutic Discovery), Perkins (Translational Cancer Research Program in Oncology), Monash (Monash Organoid Program & Monash Genome Modification Platform), MCRI (iPSC derivation & Gene Editing Facility), Peter Mac (Victorian Centre for Functional Genomics), UMelb (Centre for Stem Cell Systems & Stem Cell Disease Modelling Laboratory), UQ (In vitro Genome Engineering and Disease Modelling Service), and VCCRI (Stem Cell Production Facility iPSC Reprogramming Service)
