Glaucoma is a group of eye conditions that damage the optic nerve, which can lead to irreversible vision loss and blindness in older adults. The optic nerve is vital for good vision as it sends visual information from the eye to the brain. Damage to the optic nerve from glaucoma is often caused by build-up of high pressure from the fluid inside the eye called aqueous humor.
Aqueous humor usually drains through a tissue called trabecular meshwork, located at the angle where the iris and cornea meet. When the eye makes too much of the fluid or the drainage system does not work properly, eye pressure may increase and eventually damage the retinal ganglion cells (RGCs) and their axons, which bundle together to form the optic nerve.
Once the delicate nerve cells deteriorate, vision loss begins, but often this goes undiagnosed until significant vision loss has already occurred. Currently available treatments for glaucoma aim to lower the eye pressure through eye drops, laser treatment, or surgery, as vision once lost to glaucoma cannot be restored. None of the prevailing treatments effectively protect RGCs from harm. This gap in treatment highlights the urgent need for neuroprotective strategies that can preserve these critical nerve cells.
Scientists are now closer to identifying a biomarker that may allow doctors to detect the disease much earlier and develop new ways to protect the eye.
Researchers at the University of Missouri in the United States recently discovered that glaucoma patients have lower levels of two naturally occurring molecules, agmatine and thiamine, in their aqueous humor, compared with individuals without the disease. These small molecules, known as metabolites, may serve as early signs that can be detected through testing, offering hope for new glaucoma therapies.
Pre-clinical research by the team suggests that agmatine and thiamine may help protect RGCs and maintain visual function, offering neuroprotective potential. These molecules could eventually be developed into treatments, possibly in the form of eye drops or supplements, that slow or prevent vision loss from glaucoma. While more work needs to be done, the researchers are excited about the immense potential that their findings could trigger in future.
In an unrelated research but on the same topic of preventing the development of blindness from glaucoma, scientists have developed a novel approach that allows stem cells to be turned into retinal ganglion cells (RGCs) that are capable of migrating and surviving in the eye’s retina. This approach presents a promising new glaucoma treatment strategy as the loss of RGCs have been identified as the main cause that leads to the irreversible vision loss in glaucoma.
Earlier studies have looked at replacing RGCs through cell transplants, but this process is still in the research and development stage and fraught with limitations that highlight a need for a more precise manner of effectively repopulating these cells in the retina. Now, a multidisciplinary team led by researchers at the Schepens Eye Research Institute at Harvard Medical School in the US has identified a promising new strategy for glaucoma cell replacement therapy.
One limitation that prevents the success of current stem cell transplantation strategies in retina studies is that the majority of donor cells remain at the site of injection and do not migrate where they are most needed. To overcome this, researchers behind the new study changed the microenvironment in the eye in a way that enabled them to take stem cells from blood and turn them into RGCs cells that were capable of migrating and surviving into the eye’s retina.
The researchers created RGCs out of stem cells, then tested the ability of various signaling molecules known as chemokines to guide these new neurons to their correct positions within the retina. The research team utilized a ‘big data’ approach to examine hundreds of such molecules and receptors to eventually find 12 that were unique to RGCs. They found that ‘stromal derived factor 1’ was the best performing molecule for both migration and transplantation. The study, which was conducted on adult mouse retina, has implications that could one day be applied to the human retina.
