Skip to main content
Home

Search


NEI on Social Media | Search A-Z | en español | Text size S M L
  • About NEI
    • NEI Research Accomplishments
    • Budget and Congress
    • About the NEI Director
    • History of the NEI
    • NEI 50th Anniversary
    • NEI Women Scientists Advisory Committee (WSAC)
    • Board of Scientific Counselors
    • National Advisory Eye Council (NAEC)
    • Donating to the NEI

    Menu About NEI Block

     Contact Us

     Visiting the NIH Campus

    Mission Statement

    As part of the federal government’s National Institutes of Health (NIH), the National Eye Institute’s mission is to “conduct and support research, training, health information dissemination, and other programs with respect to blinding eye diseases, visual disorders, mechanisms of visual function, preservation of sight, and the special health problems and requirements of the blind.”

  • News & Events
    • Events Calendar
    • NEI Press Releases
    • News from NEI Grantees
    • Spokesperson bios
    • Statistics and Data
    • Resources for the media

    Pressroom Contacts

    Dustin Hays - Chief, Science Communication
    dustin.hays@nih.gov

    Kathryn DeMott, Media Relations
    Kathryn.DeMott@nih.gov

    NEI Office of Communications
    (301)496-5248

  • Health Information
    • Clinical Studies
    • Spanish Language Information
    • Publications Catalog
    • Photos and Images
  • Grants and Funding
    • Extramural Research
    • Division of Extramural Science Programs
    • Division of Extramural Activities

    Extramural Contacts

    National Eye Institute
    Division of Extramural Research
    6700B Rockledge Dr., MSC 6914
    Bethesda, MD 20892
    (FedEx, UPS, and other courier services use: Bethesda MD 20817)
    301-451-2020

  • Research at NEI
    • Office of the Scientific Director
    • Office of the Clinical Director
    • Laboratories, Sections and Units
    • eyeGENE
    • Division of Epidemiology and Clinical Applications

    Office of the Scientific Director

    Sheldon S. Miller, Ph.D., Scientific Director
    David M. Schneeweis, Ph.D., Deputy Scientific Director

    Office of the Clinical Director

    Brian P. Brooks, M.D, Ph.D., Clinical Director
    Emily Y. Chew, M.D., Deputy Clinical Director

  • Education Programs
    • National Eye Health Education Program (NEHEP)
    • Diabetic Eye Disease Education Program
    • Glaucoma Education Program
    • Low Vision Education Program
    • Hispanic/Latino Program
    • Vision and Aging Program
    • African American Program
  • Training and Jobs
    • Jobs
    • NEI Summer Intern Program
    • Diversity In Vision Research & Ophthalmology (DIVRO)
    • Student Training Programs

    To search for current job openings visit HHS USAJobs

Home » Researchers unlock regenerative potential of cells in the mouse retina
Listen

Researchers unlock regenerative potential of cells in the mouse retina

NEI-funded researchers use a clue from zebrafish to discover the cues that reprogram Müller glia into retinal neurons
Date: 
07/26/17
Press Release
mouse retina

Cells within an injured mouse eye can be coaxed into regenerating neurons and those new neurons appear to integrate themselves into the eye’s circuitry, new research shows. The findings potentially open the door to new treatments for eye trauma and retinal disease. The study appears in the July 26 issue of Nature, and was funded in part by the National Eye Institute (NEI), part of the National Institutes of Health.

“The findings are significant because they suggest the feasibility of a novel approach for encouraging regeneration in the mammalian retina, the light sensitive tissue at the back of the eye that dies in many blinding diseases,” said Tom Greenwell, Ph.D., program director at NEI. “Importantly, the investigation also demonstrates that newly generated cells in the mouse retina not only look and behave like neurons, they also wire correctly to the existing neural circuitry at the back of the eye.”

The study’s lead investigator, Tom Reh, Ph.D., and his team at UW Medicine in Seattle, looked to the zebrafish for clues about how to encourage regeneration in the mouse eye. When a zebrafish injures its eye, cells within the eye naturally regenerate, allowing the fish to maintain vision. Mammals lack this regenerative ability.

In studying zebrafish the research team homed in on Müller glia, a type of retinal cell that supports the health and functioning of neighboring neurons, and that also exhibits an innate regenerative ability. Sometimes referred to as the stem cells of the zebrafish eye, Müller glia are the cells from which all other types of retinal cells are regenerated in the fish.

Earlier research from Reh’s lab showed that in newborn mice, Müller glia can be directed to become retinal neurons by activating a transcription factor called Ascl1, which in turn activates a suite of genes involved in regeneration. By the time the mice reach adulthood, however, regions of the genetic code that are targeted by Ascl1 and that are required for regeneration become inaccessible. In other words, in adult mice, regions of the genetic code that are critical for regeneration are closed for business.

Nikolas Jorstad and Matt Wilken, graduate students in Reh’s lab, screened a library of small molecules to find one that could reopen access to the genetic code in the adult mouse.

“We found that the commonly used anti-cancer agent trichostatin A (TSA) made critical regions of DNA accessible again. Ascl1 could then bind to those regions, which stimulated the regeneration of neurons in the adult mice,” Jorstad said.

The researchers used an adult mouse model genetically engineered to express Ascl1 in Müller glia in response to tamoxifen, a commonly used breast cancer drug. In this engineered mouse, the green fluorescent protein (GFP) gene is inserted next to Ascl1, so that all cells expressing Ascl1 are labeled fluorescent green. Tamoxifen turns on Ascl1, and GFP tracks the cells where Ascl1 is expressed.

The researchers injured the mice retinas with a toxin that causes cell death in retinal ganglion cells and interneurons, another type of retinal cell whose job it is to transmit signals from photoreceptors to the brain. They then injected the mice with TSA and tamoxifen. Over the next several weeks, the shape and behavior of the fluorescent green-labeled cells were observed to see if there was evidence of regeneration.

Proteins expressed by the observed cells were similar to those of interneurons. Analyses of genome structure further shored up evidence that the cells that were once Müller glia had been genetically reprogrammed and were now showing characteristics of interneurons.

Next, teaming up with electrophysiologists William Grimes, Ph.D. and Fred Rieke, Ph.D. of UW Medicine, they looked at the cells’ electrophysiological activity in the presence of light, taking advantage of the fact that Müller glia respond to light in a distinct, measurable pattern. About two weeks following injury, the cells responded to light as if they were interneurons.

“We’re showing for the first time that Müller glia in the adult mouse can give rise to new neurons after injury, and these neurons have the gene expression pattern, the morphology, the electrophysiology, and the epigenetic program to look like interneurons instead of glia,” Reh said.

The studied cells had formed functioning synapses – connections from one neuron to another – and responded to light in a way that’s typical of a type of interneuron. The cells had also integrated with retinal cells that convey signals to the brain.

“These findings suggest that the regenerated cells were making synapses and integrating into both sides of the circuitry, presynaptically and postsynaptically,” Reh said.  

Reh envisions this approach could be useful for treatment of acute eye injuries and central retinal arterial occlusion – a stroke of the eye. The next step is to boost Müller glia numbers.

“Retinal injuries and blinding diseases of the retina tend to cause a massive loss of neurons. We need a way to stimulate the regeneration of Müller glia, in addition to strategies for coaxing them to differentiate into other types of neurons,” Reh explained.

Strategies are also needed to regenerate photoreceptors and ganglion cells, still other types of retinal cells that are lost in degenerative eye diseases such as glaucoma and macular degeneration. Reh’s lab is investigating other types of regenerative strategies to address all the retinal cell types.

NEI funding included grants R01EY021482, R01EY14358, and P30EY01730.

Reference:

Jorstad, NL., et al. 2017. Stimulation of functional neuronal regeneration from Müller glia in adult mice. Nature DOI: 10.1038/nature23283

 

###

NEI leads the federal government’s research on the visual system and eye diseases. NEI supports basic and clinical science programs to develop sight-saving treatments and address special needs of people with vision loss. For more information, visit https://www.nei.nih.gov.

About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov/.

NIH…Turning Discovery Into Health®

 

Contact: 
Full Name: 
Viviane Callier or Joe Balintfy
Email : 
NEInews@nei.nih.gov
Phone No.: 
301-496-5248
Topics: 
Retina
Tags: 
eye
regeneration
zebrafish
blindness
ocular trauma
Muller cell
epigenetics
  • NEI Home
  • Contact Us
  • A-Z Site Map
  • NEI on Social Media
  • Information in Spanish (Información en español)
  • Website, Social Media Policies and Other Important Links
  • NEI Employee Emergency Information
  • NEI Intranet (Employees Only)
  • Department of Health and Human Services
  • The National Institutes of Health
  • USA.gov

*PDF files require the free Adobe® Reader® software for viewing.

Technical questions about this website can be addressed to the NEI Website Manager.