Getting a damaged optic nerve to regenerate is vital to restoring vision in people blinded through nerve trauma or disease. A variety of growth-promoting factors have been shown to help the optic nerve’s retinal ganglion cells regenerate their axons, but we are still far from restoring vision. A new study published yesterday in Neuron underscores the complexity of the problem.
A research team led by Fengfeng Bei, PhD, of Brigham and Women’s Hospital, Zhigang He, PhD, and Michael Norsworthy, PhD, of Boston Children’s Hospital, and Giovanni Coppola, MD, of UCLA conducted a screen for transcription factors that regulate the early differentiation of RGCs, when axon growth is initiated. While one factor, SOX11, appeared to be critical in helping certain kinds of RGCs regenerate their axons, it simultaneously killed another type — alpha-RGCS (above)— when tested in a mouse model.
At least 30 types of retinal ganglion cell message the brain via the optic nerve. “The goal will be to regenerate as many subtypes of neurons as possible,” says Bei. “Our results here suggest that different subtypes of neurons may respond differently to the same factors.”
When Zhigang He, PhD, started a lab at Boston Children’s Hospital 15 years ago, he hoped to find a way to regenerate nerve fibers in people with spinal cord injury. As a proxy, he studied optic nerve injury, which causes blindness in glaucoma — a condition affecting more than four million Americans — and sometimes in head trauma.
By experimenting with different growth-promoting genes and blocking natural growth inhibitors, he was able to get optic nerve fibers, or axons, to grow to greater and greater lengths in mice. But what about vision? Could the animals see? …
Nerve regeneration. From Santiago Ramón y Cajal’s “Estudios sobre la degeneración y regeneración del sistema nervioso” (1913-14). Via Scholarpedia.
First in a two-part series on nerve regeneration. Read part 2.
Researchers have tried for a century to get injured nerves in the brain and spinal cord to regenerate. Various combinations of growth-promoting and growth-inhibiting molecules have been found helpful, but results have often been hard to replicate. There have been some notable glimmers of hope in recent years, but the goal of regenerating a nerve fiber enough to wire up properly in the brain and actually function again has been largely elusive.
“The majority of axons still cannot regenerate,” says Zhigang He, PhD, a member of the F.M. Kirby Neurobiology Center at Boston Children’s Hospital. “This suggests we need to find additional molecules, additional mechanisms.”
Microarray analyses—which show what genes are transcribed (turned on) in injured nerves—have helped to some extent, but the plentiful leads they turn up are hard to analyze and often don’t pan out. The problem, says Judith Steen, PhD, who runs a proteomics lab at the Kirby Center, is that even when the genes are transcribed, the cell may not actually build the proteins they encode.
That’s where proteomics comes in. “By measuring proteins, you get a more direct, downstream readout of the system,” Steen says. …