Genes to Save

Genes to Save Generations

Eyes are the window to the world. If one loses their vision, it can have a detrimental effect on their life. Studies are being conducted to prevent vision loss and restore sight. Gene therapy is one of those studies.
Gene therapy is a sophisticated technique that can be used against various diseases. It is the process of introducing normal genes into cells to replace defective or abnormal ones with the help of a modified virus to correct the genetic disorder. It is an effective technique that can be used in the long run to prevent diseases like glaucoma that can damage the eye. It is more successful and efficient compared to the earlier treatments. For instance, before discovering gene therapy, people used to apply eye drops to treat glaucoma. The drop had to be applied daily; however, sometimes, the treatment proved to be futile. In contrast, gene therapy is only administered once every few years or once in a lifetime, and it has proven to be effective. Thus, the research in the field has given us hope that new treatments are on the horizon to prevent blindness and restore sight.
A recent study conducted by NIH's National Eye Institute found that a gene therapy that activates Calcium modulator CaMKII protects the optic nerve in mice, preventing glaucoma in patients. The report was published in Cell. The finding has become a breakthrough discovery, a way forward for developing neuroprotective therapies for glaucoma.
Glaucoma is the neurodegeneration of the optic nerve, the bundle of axons from retinal ganglion cells that aids in the transmission of signals from the eye to the brain. It is a process that initiates slow blindness in patients resulting from increased intraocular pressure. Treatments for the diseases are available; however, it only slows down vision loss by lowering elevated eye pressure.
The recently discovered gene therapy technique activates the CaMKII pathway, protecting the retinal ganglion cells from injuries. CaMKII is a pathway that regulates crucial cellular processes and functions throughout the body. Inhibition of CaMKII activity, for example, is either protective or detrimental to retinal ganglion cells, depending on the conditions. Using an antibody marker of CaMKII activity, the researchers discovered that CaMKII pathway signaling was compromised whenever retinal ganglion cells were exposed to toxins or trauma from a crush injury to the optic nerve, suggesting a correlation between CaMKII activity and retinal ganglion cell survival. Thus, National Eye Institute proved that activating the CaMKII pathway helps to protect the retinal ganglion cells. 
The researchers from National Eye Institute observed that administering gene therapy in mice just before toxic insult (which initiates rapid damage to the cells) and after optic nerve crush (which causes slower damage) increased CaMKII activity. 
They observed that 77% of retinal ganglion cells in gene therapy-treated mice survived 12 months after the toxic insult compared with 8% in control mice. Six months following optic nerve crush, 77% of retinal ganglion cells had survived versus 7% in controls.
Furthermore, boosting the CaMKII activity has protected retinal ganglion cells of glaucoma models based on elevated eye pressure or genetic deficiencies. Thus, the discovery has translated into a greater likelihood of preserved visual function, according to cell activity measured by electroretinogram and activity patterns in the visual cortex.  
Moreover, three vision-based behavioral tests also confirmed the finding. In a visual water task, the mice were trained to swim toward a submerged platform based on visual stimuli on a computer monitor. Depth perception was confirmed by a visual cliff test based on the mouse's innate tendency to step to the shallow side of a cliff. Lastly, a looming test determined that treated mice were more apt to respond defensively (by hiding, freezing, or tail rattling) when shown an overhead stimulus designed to simulate a threat than untreated mice.
"If we make retinal ganglion cells more resistant and tolerant to the insults that cause cell death in glaucoma, they might be able to survive longer and maintain their function," stated the study's lead investigator, Bo Chen, Ph.D., associate professor of ophthalmology and neuroscience at the Icahn School of Medicine at Mount Sinai in New York City.
Thus, the epic discovery, which is the first to show that activating the CaMKII pathway can protect the optic nerve, has unlocked new ways to fight glaucoma.