New research has given new insights into a severe form of age-related macular degeneration.
Photo Credit: Colin Lloyd
Scientific Frontline: Extended "At a Glance" Summary: Severe Age-Related Macular Degeneration (AMD)
The Core Concept: Researchers have identified distinct biological and molecular features linked to a severe form of age-related macular degeneration (AMD) characterized by unusual retinal deposits. This discovery indicates that AMD comprises a group of biologically distinct conditions rather than a single, uniform disease.
Key Distinction/Mechanism: By utilizing stem cell technology to convert patient skin biopsies into laboratory-grown retinal cells, researchers compared the molecular profiles of cells from patients with and without reticular pseudodrusen. They observed that patients with this severe form of AMD exhibit a distinct underlying biology, specifically involving processes that maintain cellular structure and stability.
Major Frameworks/Components:
- Reticular Pseudodrusen: Unusual subretinal deposits associated with an increased risk of progression to severe, vision-threatening AMD.
- Stem Cell Reprogramming: The conversion of adult somatic cells (skin biopsies) into induced pluripotent stem cells, subsequently differentiated into retinal cells to model human disease pathology in vitro.
- Molecular Profiling: The comparative analysis of active genes and proteins to identify variances in structural and functional cellular support.
Branch of Science: Molecular Biology, Cellular Biology, Ophthalmology, and Genetics.
Future Application: These molecular insights provide a foundation for developing precision medicine therapies targeted at specific biological subsets of AMD, shifting away from a uniform treatment methodology.
Why It Matters: AMD affects over 196 million individuals globally and is a leading cause of irreversible vision loss. Current treatments only slow disease progression after significant damage has occurred and are ineffective for a subset of patients; identifying precise biological drivers is critical for preventing blindness in high-risk populations.
Researchers have identified distinct biological features linked to a high risk of developing a severe form of age-related macular degeneration (AMD).
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 over age fifty 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 characterized by unusual deposits in the retina called reticular pseudodrusen, which are linked to a higher risk of progression to severe forms of AMD.
Researchers collected skin biopsies from more than one hundred Australians with AMD, including some with reticular pseudodrusen and others without. They then used stem cell technology 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,” said lead author Professor Alice Pébay, AM, of the School of Biomedical Sciences and Melbourne Medical School.
“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 viewing it as a group of related conditions that could require 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.”
Funding: National Health and Medical Research Council.
Published in journal: Genome Medicine
Authors: Jenna C. Hall, Kavitha Krishna Sudhakar, Maciej Daniszewski, Anne Senabouth, Carla J. Abbott, Helena H. Liang, Himeesh Kumar, Grace E. Lidgerwood, Mehdi Mirzaei, Jessica YW Ma, Trevor Atkeson, Yumiko Hirokawa, Emeline F. Nandrot, Alexander Barnett, Chantal Cazevieille, Gaël Manes, Simon Mountford, Philip Thompson, Erica L. Fletcher, Zhichao Wu, Melanie Bahlo, Brendan R. E. Ansell, Daniel Paull, Alex W. Hewitt, Robyn H. Guymer, Joseph E. Powell, and Alice Pébay
Source/Credit: University of Melbourne
Reference Number: mbio051226_01
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