An Australian study used stem cell models of the retina and optic nerve to identify a previously unknown genetic marker for glaucoma. According to the researchers, this finding opens up a new possible treatment for glaucoma. Glaucoma is the leading cause of permanent blindness in the world.
Glaucoma is an eye disease caused by damage to retinal ganglion cells (neurons near the inner eye). The optic nerve is responsible for transmitting light received by the eye to the brain, so damage from glaucoma can lead to permanent blindness. The disease is expected to affect around 80 million people by 2040, yet treatments are extremely limited.
The research project was jointly led by the Garvan Institute of Medical Research in Australia, the University of Melbourne and the Glaucoma Research Center of Ophthalmology. Research linking 97 gene clusters to damage caused by the most common form of glaucoma — primary open-angle glaucoma, or POAG — reveals an important genetic component that controls how the disease strikes. POAG (Primary Open Glaucoma of Symmetry) is a complex disease that is likely genetic and currently medically impossible to prevent or reverse. The only existing treatment for POAG is to release eye pressure, which only slows the progression of the condition.
Study co-lead author Professor Joseph Powell, an academic at the University of Melbourne, told a Garvin Institute media release: “We’ve seen how the genetic causes of glaucoma work in individual cells, and how How it varies in different people.” “Current treatments only slow vision loss, but this new research is a first step toward drugs in individual cell types.”
The research associated with this discovery, published in the journal Cell Genomics, is the result of a long-term collaboration between Australian medical research centers involving the use of stem cell modeling to study complex diseases and their underlying genetic causes. According to the researchers, this is a testament to the success of the study and the strength of the methods used.
Previously, glaucoma research has been limited by the inability to non-invasively obtain optic nerve samples from participants. However, the stem cell model solved this problem because it allowed the researchers to sample the optic nerve from the skin, an easier body part to extract.
The team took skin biopsies from 183 participants, 91 of whom had advanced primary open-angle glaucoma, to collect skin cells that might be reprogrammed back into stem cells that might then be directed to become retinal cells. Of the 183 samples collected, 110 samples (54 from POAG participants) successfully transformed from skin cells to retinas, and more than 200,000 of these transformed cells were sequenced to generate a “molecular signature.”
The researchers used single-cell RNA gene sequencing to study individual cells. The sequencing creates a remarkably detailed genetic map, which looks for genetic variations that affect the expression of one or more genes — the process that turns DNA’s instructions into functional products like proteins. By identifying these key genes, it is possible to further infer the influence of genetic variants on glaucoma.
The characteristics of those with and without glaucoma were compared to identify key genetic components that control the way glaucoma attacks the retina.
Using characteristics of glaucoma patients and non-patients, the researchers first identified 312 genetic variants associated with eventually degenerating ganglion cells in POAG patients. Further analysis of genes associated with POAG linked the 97 clusters described above to the damage caused by glaucoma.
What the study means for glaucoma patients
University of Melbourne professor Alice Pébay, another co-lead author of the paper, said that by studying glaucoma in retinal cells, it was possible to create a specific background profile of the disease.
“We wanted to understand how glaucoma works specifically in retinal cells — not in blood samples — so we might identify key genetic mechanisms to target,” Babe said.
“Similarly, we need to know which genetic variants are healthy and normal so we can exclude them from treatment.”
It is important to develop a disease profile to advance understanding of disease causes, risks, and underlying mechanisms, the researchers note. In addition, genetic studies are crucial for drug development and preclinical testing, as they help to construct complete human disease models.
Alex Hewitt, a professor at the University of Tasmania and the paper’s third co-lead author, said the findings of the study set the stage for future research into novel glaucoma treatments. foundation.
“Not only can scientists develop more tailored drugs, but we have the potential to test hundreds of drugs in preclinical trials using stem cell models,” Hewitt said. To assess the efficacy of drugs in a way that can be used to assess whether glaucoma treatments are effective in specific patients.”
For the English report, please see the English “Epoch Times”:Secrets of Permanent Blindness Revealed by Stem-cell Research。
Editor in charge: Li Fan
