Gene Therapy Awakens the Brain Despite Blindness from Birth

University of Pennsylvania researchers have shown in an animal study that a gene therapy used to restore retinal activity to the blind also restores function to the brain's visual centre, a critical component of seeing.

Geoffrey K. Aguirre, Assistant Professor of Neurology at the university who led that multi-institutional study, feels that gene therapy can improve retinal, visual-pathway, and visual-cortex responses in animals born blind, and that it has the potential to do the same in humans.

"The retina of the eye captures light, but the brain is where vision is experienced," Aguirre said.

"The traditional view is that blindness in infancy permanently alters the structure and function of the brain, leaving it unable to process visual information if sight is restored. We've now challenged that view," he added.

According to the researchers, the new findings are significant because they support the potential for human benefit from retinal therapies aimed at restoring vision to those with genetic retinal disease.

During the course of study, the researchers used functional MRI to measure brain activity in blind dogs born with a mutation in gene RPE65, an essential molecule in the retinoid-visual cycle. The same mutation causes a blindness causing eye-retinal disorder in humans called Leber congenital amaurosis (LCA).

When the researchers performed gene therapy on canines by introducing a working copy of RPE65 into their retina, the eye functions were restored in them. However, it was unclear whether the brains of the animal could "receive" the restored sight.

The researchers noted that gene therapy to the eye dramatically increased responses to light within the visual cortex of the canine brain. They observed the recovery of visual brain function in a dog that had been blind for the first four years of its life, and the recovery persisted in another dog for at least two-and-a-half years after therapy, suggesting a level of permanence to the treatment.

Aguirre's team then studied the structure and function of the visual brain of human patients with the same form of blindness. It was found that, while the visual cortex of the patients did not respond to dim lights, their brain's reaction to brighter lights was comparable to that of individuals with normal sight.

"It seems these patients have the necessary brain pathways ready to go if their eyes start working again," Aguirre said.

"Existence of functional potential both in the eye and brain are prerequisites for successful gene therapy in all forms of LCA. In the RPE65 form of the disease, we now have evidence for both, and treatment at the retinal level has the hope of recovery of useful vision in patients," added Artur V. Cideciyan, research associate professor of ophthalmology.

Source-ANI
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