Retina and its circuits are much more pliable than scientists previously thought

A new Oregon Health & Science University study is opening scientists' eyes to the retina's ability to rewire itself so it can adapt to different levels of ambient light.

The study, published this month in the journal Neuron, and funded by a research grant from the National Eye Institute, National Institutes of Health, shows that the retina and its circuits are much more pliable than scientists previously thought.

"The retina has generally been thought of as a fixed circuitry where there shouldn't be much plasticity," said study co-author Henrique von Gersdorff, Ph.D., adjunct associate professor of cell and developmental biology, OHSU School of Medicine, and scientist at the Vollum Institute.

"But more and more people are finding that the retina does a lot of parallel things at the same time. For example, the direction of motion of objects that are moving into a visual scene is first detected in the retina and then transmitted to the brain."

The retina is a thin, light-sensitive sheet of neurons in the back of the eye that encodes three basic features of the objects in our environment – color, shape and motion – and sends the coded information to the brain. The early processing steps for vision, therefore, occur in the retina. Deep inside this sheet of interconnected neurons, at a depth called the inner plexiform layer, a tremendous processing of this visual information takes place, before it is projected to the brain through the optic nerve.

Small nerve cells called amacrine cells help bipolar cell terminals filter the bombardment of signals being sent by photoreceptors to bipolar cells before they're forwarded on to other nerve cells, called ganglion cells, which directly connect to the brain. This filtering process in the inner plexiform layer is believed to contribute to fundamental features of vision, such as sensitivity to light, temporal processing of motion, and detection of contrast.

The new study by Jozsef Vigh, Ph.D., postdoctoral fellow at the Vollum and lead investigator, examined the retinas of goldfish, which contain large nerve cells that are easier to observe. It found that the ribbon-like connections between the amacrine and bipolar cells, called synapses, can become altered during sudden changes in ambient light. This change, known as plasticity, occurs during exchanges of amino acids that serve as signals between the cells and has long-term duration: It can last as long as 10 minutes.

Until now, the flow of information occurring in these "reciprocal" synapses or junctions between bipolar cell terminals and amacrine cells hasn't been understood. "There's a transformation there of the signal, but it wasn't thought that it would involve any long-term plasticity," von Gersdorff said.

The new findings suggest that such "long-term plasticity" might be involved in certain "adaptational processes."

"When we go from a very dark room to one full of light, we need some time to adapt to those new light conditions. Initially, in fact, we are 'blinded' by the light. Perhaps, then, the retina needs to be sort of rewired for the new conditions. There needs to be some plasticity so it can operate over very different ambient light levels," von Gersdorff said. "On a cellular level, there's an adaptation, but there might also be adaptation at the circuitry level, at the synaptic level, and that's what we're proposing could be the case."

The study's results may be useful in future efforts to develop prosthetic retinal devices that allow changes in light to trigger spike signals within ganglion cells, allowing people who are blind to distinguish shapes, von Gersdorff said.

"We're still in the very early days of understanding the retina. There's so much we don't know about the circuitry, how it functions and the properties, so our lab is basically trying to figure out some basic properties and hopefully that knowledge will help in curing diseases," he said. "If you understand how something normally works, you can then try to understand how dysfunction occurs."