The ‘eyes’ have it When our optic nerve is damaged – by glaucoma or diabetic neuropathy, for example – it’s basically game-over for our eyesight. The nerve can’t be healed and our vision loss can’t be restored. But that’s not the case with fish, which can regenerate their optic nerve in 12 days and regain their eyesight after an additional 80 days after an injury. UWM biologist Ava Udvadia just figured out how they do it, and she hopes that discovery will lead to treatment for eye ailments in humans. Of injured eyes and growing cells A nerve cell, or neuron, consists Ava Udvadia of three major parts: A body, which contains the nucleus of the cell; dendrites, which receive incoming information; and an axon, a “tail’ that connects the neuron to cells in another part of the body to transmit information. The optic nerve contains the axons of neurons that transmit visual information from the eye to the brain. In the type of eye injuries Udvadia is studying, the initial injury is to the axons, while the cell bodies remain intact for a while. In order to repair the injury, the neurons need to regenerate their axons and reestablish connections with the brain. That’s impossible for fully mature neurons in the central nervous system of mammals, which are locked into their current state. It’s not impossible for developing neurons, however, which got Udvadia thinking about how to reprogram damaged adult neurons. “Nobel prize-winning work on induced pluriopotent stem cells showed us that you can take a take a fully differentiated cell from an adult tissue and you could
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actually reprogram it – that is, back it up to a state where now, it could give rise to any type of cell in the body,” Udvadia said. “With a damaged optic nerve, we don’t want to back the neurons up that far. We want to keep them as neurons, but back them up to a state where they can rewire their connections to the brain. Fish can do it, mammals can’t. Why not?” A good question, especially since fish and humans use similar programming to initially wire the visual system during development. That is, the same genes tell neurons to grow their extensions during development and to stop growing in adults. The difference between fish and humans is in the ability to turn the growth program back on after injury in adults. The answer, Udvadia thinks, is in the arrangement of each species’ genetic information. This arrangement enables fish to “turn on” a genetic program that regenerates their nerve. The arrangement in mammals prevents the reactivation of the axon growth program. A novel approach to experimenting To understand how fish regenerate their optic nerves, Udvadia and her team took a different approach. “In the past, people looked at regeneration as a single event. Our approach looked at it as actually being a series of events,” Udvadia said. “We know in development as the neuron is growing to make its connections – very specifically, the neurons in the eye making this connection to the brain – it has to go through a lot of different and complex environments.” She and her team looked at several key points in the fish’s regeneration timeline: 1. The injured neuron first has to grow past the site of the initial injury. 2. The neuron has to choose the correct crossroads when its connection reaches the juncture of the
