Stem cell models reveal glaucoma secrets

Image shows Professor David Mackey in the research lab wearing bright orange safety gloves and opening a freezer.

Professor David Mackey AO in the Lions Eye Institute research laboratory


Australian researchers uncover hidden genetic markers of glaucoma

Professor David Mackey AO from the Lions Eye Institute is one of a team of researchers that has published their exciting research into stem cell models of the retina and optical nerve. The stem cell models have been used to identify previously unknown genetic markers of glaucoma.

“This important national glaucoma collaboration grew retinal ganglion cells from the stem cells of glaucoma patients to discover which genes are specifically involved in the cells that die in glaucoma,” says Professor Mackey. The research opens the door to new treatment for glaucoma, which is the world’s leading cause of permanent blindness.

The research, published recently in the journal Cell Genomics, was jointly led by Professor Joseph Powell from the Garvan Institute of Medical Research, Professor Alice Pébay from the University of Melbourne and Professor Alex Hewitt from the Centre for Eye Research Australia and the Menzies Institute for Medical Research at the University of Tasmania.

Glaucoma damages cells in the optic nerve, the part of the eye that receives light and sends it to the brain. It is impossible to take samples from this part of the eye in a non-invasive way, which limits research. Instead, to create samples for the study, researchers took skin biopsies from participants with and without glaucoma. The skin cells were reprogrammed to revert to stem cells, and then guided into becoming retinal cells.

With 110 successfully converted samples, researchers sequenced more than 200,000 individual cells to generate ‘molecular signatures’. Comparing signatures with and without glaucoma revealed key genetic components that control how the disease attacks the retina. 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.

About glaucoma

Glaucoma is the leading cause of blindness worldwide and is predicted to affect about 80 million people by 2040. Treatments options are currently extremely limited. The most common form of glaucoma (primary open-angle glaucoma, or POAG) causes the degeneration of retinal ganglion cells, which are neurons near the inner eye. This leads to a gradual and irreversible loss of vision.

POAG is likely to be inherited from a parent and is a very genetically complex disease. The only available treatment is to release pressure in an affected eye, which slows the loss of sight but can’t stop or reverse the process.

About gene profiling

The researchers used single-cell RNA genetic sequencing to examine individual cells, which creates a very detailed genetic ‘map’.

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.

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