Stem cell models of the retina and optical nerve have been used to identify previously unknown genetic markers of glaucoma, in research jointly led by scientists from the Garvan Institute of Medical Research, the University of Melbourne, and the Centre for Eye Research Australia. The findings open the door to new treatment for glaucoma, which is the world’s leading cause of permanent blindness.
“We saw how the genetic causes of glaucoma act in single cells, and how they vary in different people. Current treatments can only slow the loss of vision, but this understanding is the first step towards drugs that target individual cell types,” says Professor Joseph Powell, joint lead author at the Garvan Institute of Medical Research.
The research, published today in the journal Cell Genomics, comes out of a long-running collaboration between Australian medical research centres to use stem-cell models to uncover the underlying genetic causes of complicated diseases.
The researchers used single-cell RNA genetic sequencing to examine individual cells, which creates a very detailed genetic ‘map’.
This research is possible due to advances in three key areas: the development of single-cell sequencing technology that shows relationships between individual cells; the ability to produce, reprogram and differentiate stem cells at scale; and advances in machine learning to analyse the incredible data sets.
Profiling complicated genetic diseases such as glaucoma improves our understanding of its underlying mechanisms, possible causes and risk factors.
The researchers used a kind of genetic mapping which looks for genetic variations that affect the expression of one or more genes. Identifying these key genes can be used to further deduce how common genetic variations influence glaucoma.
Genetic investigations help build complete human models of disease, which are crucial for drug development and pre-clinical trials. The success of this research highlights the power of large-scale studies using stem-cell models to uncover new genetic indicators of specific diseases.
Across both healthy and diseased samples, researchers identified 312 genetic variants associated with the target retinal cells. Further analysis found 97 genetic clusters linked to the damage caused by glaucoma.
The study’s third lead author, Professor Alex Hewitt, says the findings lay the foundation for research into new glaucoma treatments:
“Not only can scientists develop more tailored drugs, but we could potentially use the stem-cell models to test hundreds of drugs in pre-clinical assays. This method could also be used to assess drug efficacy in a personalised manner to assess whether a glaucoma treatment would be effective for a specific patient.”
Source – Garvan Institute of Medical Research
Daniszewski M, Senabouth A, Liang HH et al. (2022) Retinal ganglion cell-specific genetic regulation in primary open-angle glaucoma. Cell Genomics 2(6), 100142. [article]
