Gene Therapy Strengthens the Retina’s Connection to the Brain

While we often think of the retina as that magical piece of tissue lining the back of the eye that makes vision possible, the brain is also an essential partner in the visual process. When light comes into the eye and is converted to electrical signals, those signals are sent through the optic nerve to the back of the brain, where they are transformed into the images we see. When children are born, pathways between the retina and the brain are in place, and, with increased interaction with the world, they become stronger over time.

However, if a child is born with severe vision loss from a retinal disease like Leber congenital amaurosis (LCA), these pathways don’t develop normally due to lack of retinal input. They also further deteriorate as the retina degenerates.

Since we see with our eyes and the brain, researchers have wondered what happens to the brain when the eye can’t see. More interestingly, what happens to the brain when the eye is enabled to see through gene therapy? Would the brain and eye restart their partnership? Would this handshaking happen for humans of all ages? Would the brain be able to harness the visual-processing pathways later in life?

Thanks to Manzar Ashtari, Ph.D., who is leading groundbreaking, brain-imaging studies at the University of Pennsylvania and The Children’s Hospital of Philadelphia (CHOP), we now know the answer is yes. Published in the journal Science Translational Medicine, and funded in part by the Foundation Fighting Blindness, her research shows that retina-brain pathways can be established in LCA patients not only after decades of near blindness, but that they are strengthened with use after the retina has been treated.

This is exciting news, because researchers were concerned that the brain’s plasticity—its ability to develop and respond to the new input from the retina—would be lost. The study shows that the brain has the capacity to adapt to retinas with improved function thanks to gene therapy. This not only bodes well for people with LCA; it is good news for others who might receive gene therapy later in life for an early-onset retinal disease.

Dr. Ashtari used advanced magnetic resonance imaging techniques that examine the deeper brain layers to observe that eyes treated with gene therapy had a stronger connection to the brain than untreated eyes. She is continuing her comprehensive imaging studies to better understand the brain structure and function of the LCA patients before and after treatment.

Meanwhile, the Phase III LCA gene-therapy clinical trial at CHOP and the University of Iowa is moving full steam ahead with children as young as 3 receiving the treatment. Also, all patients in the trial are having both eyes treated. If all continues to go well, the trial’s sponsor, Spark Therapeutics, could seek approval for the gene therapy from the U.S. Food and Drug Administration in less than two years.