Stem cell models of the retina and optic nerve was used to identify previously unknown genetic markers of glaucoma in a joint study by scientists from the Garvan Institute of Medical Research, the University of Melbourne and the Australian Eye Research Center. perform. The discovery has opened the door to new treatments for glaucoma, the world’s leading cause of permanent blindness.
Professor Joseph Powell. Image credit: Garvan . Institute
“We have seen the genetic cause of Glaucoma work in single cells and how they differ in different people. Current treatments can only slow vision loss, but this understanding is the first step toward drugs that target individual cell types,” Professor Joseph Powelllead author at Garvan.
The study was published in the journal Cell genomestemming from a longstanding collaboration between Australian medical research centers to use stem cell models to uncover the underlying genetic causes of complex diseases.
Glaucoma damages cells in the optic nerve, the part of the eye that receives light and sends it to the brain. It is not possible to obtain a sample from this part of the eye in a non-invasive way, which limits the study.
Instead, to model the study, the researchers took skin biopsies from participants with and without glaucoma. Skin cells are reprogrammed to become stem cells, and then instructed to become retinal cells.
With 110 successfully converted samples, the researchers sequenced more than 200,000 individual cells to generate ‘molecular signatures’. Comparison of markers with and without glaucoma reveals important genetic components that control how the disease attacks the retina.
Studying glaucoma inside retinal cells has created a ‘context-specific profile’ of the disease that is extremely complex, said Professor Pébay, co-lead author.
“We wanted to see specifically how glaucoma works in retinal cells – rather than in a blood sample – to identify important genetic mechanisms for targeting. Similarly, we need to know which genetic variants are healthy and normal, so we can rule them out from a treatment,” she said.
Across both healthy and diseased samples, the researchers identified 312 genetic variants associated with target retinal cells. Further analysis found 97 genetic clusters that were associated with glaucoma-induced damage.
The study’s third lead author, Professor Alex Hewitt, said the findings lay the groundwork for the study of new glaucoma treatments:
“Scientists can not only develop more tailored drugs, but can also use stem cell models to test hundreds of drugs in preclinical trials. This approach can also be used to assess drug effectiveness in an individualized way to assess whether glaucoma treatment is effective for a particular patient. ”
About Glaucoma
Glaucoma is the leading cause of blindness worldwide and will affect around 80 million people by 2040. Treatment options are currently very limited.
The most common form of glaucoma (primary open-angle glaucoma, or POAG) causes degeneration of the retinal ganglion cells, the nerve cells near the inner eye. This leads to gradual and irreversible loss of vision.
POAG is likely to be inherited from parents and is a very complex genetic disease. The only treatment available is to release pressure in the affected eye, which slows vision loss but cannot stop or reverse the process.
Introduction to gene configuration
The researchers used single-cell RNA gene sequencing to examine individual cells, creating a detailed genetic ‘map’.
This research was made possible by advances in three key areas: the development of single-cell sequencing technology that demonstrates relationships between individual cells; the ability to produce, reprogram and differentiate stem cells on a large scale; and advances in machine learning to analyze incredible data sets.
The profile of complex genetic diseases such as glaucoma helps us to better understand its underlying mechanisms, possible causes, and risk factors.
The researchers used a type of genetic map to look for genetic variations that affect the expression of one or more genes. The identification of these important genes can be used to further infer how common genetic variants affect glaucoma.
Genetic investigations help build complete human disease models, which are important for drug development and preclinical testing. The success of this study demonstrates the power of large-scale studies using stem cell models to uncover novel genetic markers of specific diseases.
Source: Garvan Institute
