Mason Offers Lessons in Axon Guidance for Binocular Vision
Retinal neurons are programmed to migrate to one side of the brain or the other during development. Dr. Carol Mason of Columbia University, who recently visited NIH, has discovered elements of this programming. Understanding the factors that guide neurons to their appropriate targets could someday help doctors rebuild damaged visual circuitry in the brain.
Millions of years ago, sometime between the appearance of fish and frogs on the planet, animals’ connections between the eyes and the brain transitioned from a simple crisscross (right eye to left brain, and vice versa) to a more complex arrangement. Binocularity, as it’s called, evolved when each eye began connecting to both sides of the brain, enabling the brain to merge input from both eyes into a single image. Increased binocularity is found in animals, including humans, with eyes close together on the front of the head, and is needed for depth perception.
During development, neurons grow out of the retina toward the brain, passing through a zone known as the chiasm. In certain animals such as fish, all neurons from the retina are contralateral, meaning they cross the chiasm. In higher-order species, including mice and humans, a subset of retinal neurons do not cross the chiasm, instead connecting to the same side of the brain as the eye from which they originate. These are called ipsilateral neurons.
For Mason, there are two big questions: How are contralateral and ipsilateral neurons different? And what factors determine the direction neurons go when they reach the chiasm? Using mice, she found that the neurons destined to cross the chiasm carried one set of protein markers on their surfaces, while those programmed to reverse course carried a distinct set of protein marker the ipsilateral neurons while allowing the contralateral neurons to pass through.
Each group of neurons—generally depending on where they start in the retina—are pre-programmed to become contralateral or ipsilateral. But, curiously, in people lacking the tyrosinase gene, some ipsilateral neurons cross the chiasm incorrectly. These people end up with too many contralateral neurons, which results in poor stereo vision (including reduced depth perception). By tracking individual neurons, Mason discovered that a specific group of neurons, originating from a particular region of the retina, are the ones that lose their way.
Tyrosinase isn’t involved directly in neuron growth or the chiasm. Instead, tyrosinase is critical for producing melanin, the pigment found in skin and in retinal epithelial cells.
“It’s still a mystery,” said Mason. “Why does the absence of melanin produce a reduction in the ipsilateral pathway?”
Understanding how these neurons connect is critical for understanding how to rebuild those connections after the retina has degenerated from diseases such as glaucoma and age-related macular degeneration.
“The one big bugaboo in all of retinal regeneration in vivo,” said Mason, “is that nothing can get through the optic chiasm in the adult.” Knowing how these neurons find their way could be key to restoring vision in adults who have lost their sight.