Building a Wiring Diagram for the Retina to Help Researchers Save and Restore Vision
Understanding the pathways of the retinal neural network — and how they are rewired with aging and disease — is helpful in trying to save and restore vision.
An image of an electrically connected patch of one single class of retinal neurons that signal brightness for the visual system. Each single cell is shaped like a spider or octopus and connected to its neighbors. This is the first visualization of such a population of cells that has been untangled from the complete connectome.[/caption] In simple terms, the retina is a thin, delicate layer of tissue lining the back of the eye that captures light like film or digital sensors in a camera. But the retina is actually an incredibly complex network of hundreds of millions cells that process light, converting it into electronic signals, which are sent to the brain and used to create the images we see. And, understanding the pathways of this gargantuan network — and how they are rewired with aging and disease — is helpful in trying to save and restore vision. "If you are going to fix cells in the retina, you have to know how they communicate," said Robert E. Marc, Ph.D., University of Utah, in the opening keynote lecture at the RD2016 meeting in Kyoto, Japan. Held September 19-24, RD2016 is the largest research conference dedicated exclusively to retinal degenerations, and funded in part by the Foundation Fighting Blindness.
Dr. Marc and his colleagues have led the way in documenting the retina's "connectome," which he referred to as "the complete wiring diagram for the retina." The size of the human retina's connectome — or the number of pathways — is mind-blowingly large: 9 x101478. That's a nine followed by 1478 zeroes!
"We are on a quest to understand the networks that encode color, form, motion, texture," explained Dr. Marc. "Ultimately, we want to understand what happens when these networks engage in faulty rewiring or fail when neurons die in retinal degenerations."
The key problem in analyzing a connectome is the mathematical diversity of the network. Dr. Marc said that finding and understanding the correct network is daunting, like decoding a new language.
Thus far, Dr. Marc and his team have built connectomes for the retinas of mice and rabbits, including a rabbit that is genetically engineered to have retinitis pigmentosa. They are currently working on a retinal connectome for a non-human primate, and plan to build one for humans.
"It takes about two years to build a connectome and several years to analyze it," said Dr. Marc. "We have already homed in on several wiring anomalies for the rabbit model of RP and are working to understand how retinalprosthetics — that is, bionic retinas — interact with remodeled retinas." All these efforts take a long time, because of the enormity and complexity of the networks.