Untangling the complex puzzle of optic nerve regeneration

June 21, 2017, Brigham and Women's Hospital
Cells, genetically marked with GFP, are viewed on a flat-mounted retina. The axons or fibers lead to the optic nerve head (round structure in the top right corner) and then exit the eyeball into the optic nerve. The alpha RGCs are killed by sox11 despite its pro-regenerative effect on some other still undefined type(s) of RGCs. Credit: Fengfeng Bei, Brigham and Women's Hospital

The optic nerve is vital for vision—damage to this critical structure can lead to severe and irreversible loss of vision. Fengfeng Bei, PhD, a principal investigator in the Department of Neurosurgery at Brigham and Women's Hospital, and his colleagues want to understand why the optic nerve—as well as other parts of the central nervous system including the brain and spinal cord—cannot be repaired by the body. In particular, Bei's lab focuses on axons, the long processes of neurons that serve as signaling wires.

In a new study published in Neuron, Bei, Michael Norsworthy in Zhigang He's lab at Boston Children's Hospital and colleagues report on a transcription factor that they have found that can help certain neurons regenerate, while simultaneously killing others. Unraveling exactly which signals can help or hinder axon regeneration may eventually lead to new and precise treatment strategies for restoring vision or repairing .

"Our long term goal is to repair brain, spinal cord or eye injury by regenerating functional connections," said Bei. "The goal will be to regenerate as many subtypes of neurons as possible. Our results here suggest that different subtypes of neurons may respond differently to the same factors. This may mean that when we reach the point of developing new therapies, we may need to consider combination therapies for optimal recovery."

Previous studies using the as a model for injury have found that manipulating transcription factors—the master control switches of genes - might represent a promising avenue for stimulating . In the current study, researchers focused on transcription factors likely to influence the early development of (RGCs). There are at least 30 types of RGCs in the human eye, which control different aspects of vision, and the researchers were interested in the effects of on various types of RGCs. Using a mouse model of optic nerve injury, the research team found that increasing the production of a transcription factor known as Sox11 appeared to help axons grow past the site of injury. However, the team observed that the very same transcription factor also efficiently killed a type of RGCs known as alpha-RGCs which would preferentially survive the injury if untreated.

Bei notes that the heterogeneity of the nervous system—the inclusion of different cells with different properties and functions—will be an important consideration as researchers work to reprogram and, ultimately, restore the optic nerve, brain or after injury.

Explore further: Stress pathway identified as potential therapeutic target to prevent vision loss

More information: Norsworthy M et al. "Sox11 Expression Promotes Regeneration of Some Retinal Ganglion Cell Types but Kills Others" Neuron DOI: 10.1016/j.neuron.2017.05.035

Related Stories

Stress pathway identified as potential therapeutic target to prevent vision loss

February 8, 2012
A new study identifies specific cell-stress signaling pathways that link injury of the optic nerve with irreversible vision loss. The research, published by Cell Press in the February 9 issue of the journal Neuron, may lead ...

Axon regeneration in response to nervous system injury

May 4, 2017
Alexandra Byrne, PhD, assistant professor of neurobiology, is working to identify which genes control how the nervous system responds to injury. Specifically, the Byrne lab at UMMS is working to identify the genes that prevent ...

Researchers compare neurons in optic nerves to find why some regenerate and others don't

May 5, 2015
It's a question that seems to offer tantalizing hope to those suffering from vision impairment. Why is it that when the optic nerve is damaged—either through trauma or disease—few of its neurons survive and fewer still ...

Zinc: A surprise target in regenerating the optic nerve after injury

January 3, 2017
For more than two decades, researchers have tried to regenerate the injured optic nerve using different growth factors and/or agents that overcome natural growth inhibition. But at best, these approaches get only about 1 ...

Proteomics provides new leads into nerve regeneration

May 5, 2015
Using proteomics techniques to study injured optic nerves, researchers at Boston Children's Hospital have identified previously unrecognized proteins and pathways involved in nerve regeneration. Adding back one of these proteins—the ...

Study overturns seminal research about the developing nervous system

April 20, 2017
New research by scientists at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA overturns a long-standing paradigm about how axons—thread-like projections that connect cells in the ...

Recommended for you

New study sheds light on brain's ability to orchestrate movement

May 17, 2018
To carry out any action, whether playing the piano or dancing the jitterbug, the brain must select and string together a series of small, discrete movements into a precise, continuous sequence.

Learning music or speaking another language leads to more efficient brains

May 17, 2018
Whether you learn to play a musical instrument or speak another language, you're training your brain to be more efficient, suggests a Baycrest study.

Old drug provides promising new avenue for treatment of MND

May 17, 2018
An international study led by biochemists at the University of Liverpool has shown that the drug-molecule ebselen can correct many of the toxic characteristics of a protein that causes some cases of hereditary motor neurone ...

Our brains are obsessed with being social

May 16, 2018
Our brains are obsessed with being social even when we are not in social situations. A Dartmouth-led study finds that the brain may tune towards social learning even when it is at rest. The findings published in an advance ...

GABA, GABA, GABA, what does it actually do in the brain?

May 16, 2018
Gamma-Aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the brain. It is the control knob of all control knobs. But why GABA? What, if anything, might be so special about the molecule?

For older adults, a better diet may prevent brain shrinkage

May 16, 2018
People who eat a diet rich in vegetables, fruit, nuts and fish may have bigger brains, according to a study published in the May 16, 2018, online issue of Neurology, the medical journal of the American Academy of Neurology.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.