Scientists Discover Gene Therapy Might Be an Option for Glaucoma

Glaucoma is a leading cause of vision impairment and blindness, affecting 76 million patients worldwide. The optic nerve is made of more than a million tiny nerve fibers. It is like an electric cable made up of many small wires. As these nerve fibers die, people will develop blind spots in vision. These blind spots may not be noticed until most of optic nerve fibers have died. If all of the fibers die, one will become blind.

Researchers at Icahn School of Medicine at Mount Sinai, in New York City, USA, published a new research in the journal Cell on 22nd July, 2021, which has shown for the first time that activating the CaMKII pathway (calcium/calmodulin-dependent protein kinase II) helps protect retinal ganglion cells from a variety of injuries, creating a new approach to developing neuroprotective therapies for glaucoma and offering hope for those with severe vision loss due to retinal degenerative diseases.

Glaucoma is caused by irreversible degeneration of the optic nerve, the bundle of axons in the retinal ganglion cells that transmits signals from the eye to the brain to generate vision. Existing treatments slow vision loss by lowering intraocular pressure; however, some glaucoma progresses to blindness despite normal intraocular pressure. And neuroprotective therapies meet the needs of patients who lack treatment options.

The CaMKII pathway regulates key cellular processes and functions throughout the body, including the retinal ganglion cells in the eye. The team found that the CaMKII signaling pathway was compromised whenever retinal ganglion cells were exposed to toxins or trauma from optic nerve crush injury, suggesting a correlation between CaMKII activity and retinal ganglion cells.

In the search for ways to intervene, researchers confirmed that activation of the CaMKII pathway with gene therapy has a protective effect on retinal ganglion cells.

In experiments in which mice were poisoned, and their optic nerve was crushed (which causes slower cell damage), researchers transferred modified versions of CaMKII with mutant amino acids into primary mouse retinal ganglion cells via adeno-associated viral vectors and found that this gene therapy approach increased CaMKII activity and strongly protected retinal ganglion cells.

In mice treated with gene therapy, 77% of retinal ganglion cells survived 12 months after toxicity, compared with 8% of control mice. Six months after optic nerve extrusion, 77% of retinal ganglion cells survived compared to 7% of controls. The increased survival of retinal ganglion cells signifies the protection of visual function, implying that the gene therapy protects optic nerve cells and thus vision.

In addition, the researchers demonstrated that increased CaMKII activity by gene therapy had a protective effect on retinal ganglion cells in a model of glaucoma based on high intraocular pressure or genetic defects.

As a next step, the researchers will test this therapy in a larger animal model, paving the way for it to enter clinical trials.

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