Secrets of Permanent Blindness Revealed by Stem-cell Research – The Epoch Times
By daniellenierenberg
Research into the retina and optic nerve using stem-cell models has unveiled specific genetic markers of glaucomathe worlds leading cause of permanent blindness possibly opening up new treatments for the condition.
Glaucoma is a blanket term describing a group of eye conditions that do damage to the retinal ganglion cellsneurons near the inner eye that make up the optic nerve. The optic nerve is the part of the eye that receives light and transmits it to the brain; thus, the damage that glaucoma does leads to permanent blindness. Thecondition is predicted to affect around 80 million people by 2040, yet treatments are extremely limited.
This study linked 97 genetic clusters to the damage done by the most common form of glaucoma, primary open-angle glaucoma or POAG, revealing important genetic components that control the way the condition attacks. POAG is a genetically complicated condition that is likely hereditary and, at the moment, cannot be stopped or reversed. The only treatment of POAG available involves releasing pressure on the eye, and this will only slow down the condition.
The research project was led jointly by the Garvan Institute of Medical Research, the University of Melbourne, and the Centre for Eye Research Glaucoma.
We saw how the genetic causes of glaucoma act in single cells, and how they vary in different people, said joint lead author of the study and Melbourne University academic, Prof. Joseph Powell, in a Garvan Institutemedia release.
Current treatments can only slow the loss of vision, but this understanding is the first step towards drugs that target individual cell types, Powell said.
The research behind the discoverywas published in the journalCell Genomicsand wasthe result of a lengthy collaboration between Australian medical research centres involving the investigation of complicated diseases and their underlying genetic causes, using stem-cell modelling; which the researchers said demonstrated the success of this study and the power of this approach.
Previously, glaucoma research was limited because samples of the optic nerve could not be obtained from participants in a non-invasive fashion. However, stem-cell modelling addressed this issue as it allowed researchers to develop optic nerve samples from skin, a much easier part of the body to extract.
The team administered skin biopsies on183 participants, 91 of whom had advanced primary open-angle glaucoma, to gather skin cells that they could reprogram to revert into stem cells and then guide into becoming retinal cells. Of the 183 samples collected, 110 samples, 54 from participants with POAG, were successfully converted from skin cells into retinal, and over 200,000 of these converted cells were sequenced to generate molecular signatures.
The researchers of this study employedsingle-cell RNA genetic sequencing in order to study individual cells. This form of sequencing creates an incredibly detailed genetic map, which looks for genetic variations that affect the expressionthe process of turning instructions from DNA into functional products like proteins of one or more genes. Through identifying these key genes, further deductions on the influence that genetic variations have on glaucoma can be made.
The signatures of those with and without glaucoma were compared to establish key genetic components that control the way that glaucoma attacks the retina.
The researchers first identified, using the signatures of both those with and without glaucoma,312 genetic variants associated with the ganglion cells that eventually degenerate in a person living with POAG. Further analysis of the genes associated with POAG linked the 97 clusters mentioned above to the damage done by glaucoma.
Another joint-lead author of the paper and Melbourne University professor, Alice Pebay, said that by studying glaucoma in retinal cells, a context-specific profile of the disease was created.
We wanted to see how glaucoma acts in retinal cells specificallyrather than in a blood sample, for instanceso we can identify the key genetic mechanisms to target, Pebay said.
Equally, we need to know which genetic variations are healthy and normal, so we can exclude them from a treatment.
To improve the understanding of complex conditions such as glaucoma, researchers noted it was important to establish a profile of the disease which promotesthe understanding of causes, risks and fundamental mechanisms of diseases. Furthermore, genetic investigations are critical to drug development and pre-clinical trials because they assist in constructing complete human models of diseases.
University of Tasmania professor and a third joint-lead author of the paper,Alex Hewitt said that the findings of this study set up future research into novel 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, said Hewitt.
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.
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Secrets of Permanent Blindness Revealed by Stem-cell Research - The Epoch Times
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