The Proceedings of the National Academy of Sciences (PNAS) reports a major breakthrough by two Weill Cornell Medical College researchers in the longstanding efforts of restoring sight. The team managed to decipher the retina’s neural code from a mouse and coupled this information to a novel prosthetic device to restore sight to blind mice. They report that they have also deciphered the code for a monkey retina, which is more or less identical to that of humans, and hope that in the near future they can design and test a device for blind humans to use.

In contrast to currently available prosthetics that provide blind users with spots and edges of light to help them navigate, this novel device has a code to restore normal vision that is so accurate, it allows recognition of facial features and allows animals to track moving images.

Leading researcher, Dr. Sheila Nirenberg, a computational neuroscientist at Weill Cornell, hypothesizes that one day blind people may be wearing a visor similar to that used on Star Trek, which takes in light and uses a computer chip that converts the light into a code, which the brain can then translate into an image.

Dr. Nirenberg, a professor in the Department of Physiology and Biophysics, at the Institute for Computational Biomedicine at Weill Cornell, commented: “It’s an exciting time. We can make blind mouse retinas see, and we’re moving as fast as we can to do the same in humans.”

This new discovery offers hope for 25 million blind people worldwide whose blindness was caused by diseases of the retina, and whose only hope for regaining vision lies in a prosthetic device.

Dr. Nirenberg explains: “This is the first prosthetic that has the potential to provide normal or near-normal vision because it incorporates the code.”

In normal vision, light falls on photoreceptors on the retina’s surface, which is then processed by the retinal circuitry and converted into a code of neural impulses that are subsequently transmitted to the brain by the retina’s ganglion cells (output cells). The brain then translates these codes of neural impulses into meaningful images.

Diseases of the retina, which kill the photoreceptors and destroy the retinal circuitry, are common reasons for blindness. However, usually these diseases do not damage the retina’s ganglion cells. Prosthetics that are currently available typically function by driving these surviving cells. The patient’s blind eye is implanted with electrodes, which stimulate the ganglion cells with current that leads to producing rough visual fields.

A substantial amount of research is conducted into improving performance by implanting more stimulators into the patient’s eye, in the hope that these will activate more ganglion cells in the damaged tissue and improve the quality of the images produced. Other researchers are experimenting using light-sensitive proteins that are introduced into the retina by gene therapy as an alternate way to stimulate the cells. Once introduced in the eye, these proteins can target many ganglion cells at once.

Dr. Nirenberg highlights that there is another critical factor, saying: “Not only is it necessary to stimulate large numbers of cells, but they also have to be stimulated with the right code the code the retina normally uses to communicate with the brain.” This particular code is the breaking discovery that the Weill researchers have made and which they incorporated into a novel prosthetic system.

She explained that any light patterns that fall onto the retina had to be converted into a general code, a set of equations-that turns light patterns into patterns of electrical pulses. He says: “People have been trying to find the code that does this for simple stimuli, but we knew it had to be generalizable, so that it could work for anything-faces, landscapes, anything that a person sees.”

The idea of applying the code to a prosthetic occurred to Dr. Nirenberg whilst working on the code for a different reason, and she and her team immediately followed up on the idea by implementing the mathematical equations on a “chip” and combining it with a mini-projector. The chip, acts as “encoder” by converting images that enter the eye into streams of electrical impulses, whilst the mini-projector converts these electrical impulses into light impulses, which drive the light-sensitive proteins that have been introduced into the ganglion cells that in return transmit the code to the brain.

They tested their entire theory on the mouse by building two prosthetic systems, one of which had the code and the other one without. Dr. Nirenberg said: “Incorporating the code had a dramatic impact. It jumped the system’s performance up to near-normal levels-that is, there was enough information in the system’s output to reconstruct images of faces, animals-basically anything we attempted.”

After conducting a comprehensive series of experiments, they discovered that the patterns produced by the blind retinas in mice closely matched those produced by normal mouse retinas.

Dr. Nirenbeck explains: “The reason this system works is two-fold. The encoder-the set of equations-is able to mimic retinal transformations for a broad range of stimuli, including natural scenes, and thus produce normal patterns of electrical pulses, and the stimulator (the light sensitive protein) is able to send those pulses on up to the brain. What these findings show is that the critical ingredients for building a highly-effective retinal prosthetic-the retina’s code and a high resolution stimulating method-are now, to a large extent, in place.”

The novel retinal prosthetic needs to undergo human clinical trials to assess the safety of the gene therapy component that delivers the light-sensitive protein, but Nirenberg is optimistic that it is safe since similar gene therapy vectors have been successfully tested for other retinal diseases. She concludes: “This has all been thrilling. I can’t wait to get started on bringing this approach to patients.”

Dr. Nirenberg and her assistant Dr. Pandarinath have filed a patent application for the prosthetic system filed through Cornell University.

Written by Petra Rattue