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<p class="publishdate"><span property="dc:date" datatype="xsd:dateTime" content="2017-08-08T00:00:00-04:00" class="date-display-single">August 8, 2017</span></p><div class='syndicate'><h1>Regenerating retinal cells in mice</h1><div class="callout callout-with-border"><h3>At a Glance</h3>
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<li>Researchers discovered that cells within an injured mouse eye can be coaxed into regenerating neurons that integrate themselves into the eye’s circuitry.</li>
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<li>The findings may open the door to new treatments for eye trauma and retinal disease.</li>
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-large/public/news-events/research-matters/2017/20170808-retinal-cells.jpg?itok=_4e_W7mm&timestamp=1502122882 1x" media="screen and (min-width: 960px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium/public/news-events/research-matters/2017/20170808-retinal-cells.jpg?itok=HWqK9WaM&timestamp=1502122882 1x" media="screen and (min-width: 800px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium-small/public/news-events/research-matters/2017/20170808-retinal-cells.jpg?itok=tpeKgoFw&timestamp=1502122882 1x" media="screen and (min-width: 600px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-small/public/news-events/research-matters/2017/20170808-retinal-cells.jpg?itok=_BsVhd7Y&timestamp=1502122882 1x" media="screen and (min-width: 480px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-tiny/public/news-events/research-matters/2017/20170808-retinal-cells.jpg?itok=HDDU59PL&timestamp=1502122882 1x" media="screen and (min-width: 0)" />
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<img src="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium/public/news-events/research-matters/2017/20170808-retinal-cells.jpg?itok=HWqK9WaM&timestamp=1502122882" alt="Image of a mouse retina under a fluorescent microscope" title="Image of a mouse retina under a fluorescent microscope" />
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</picture><span class="caption">Regenerating Muller glia (yellow) in the mouse retina.</span><span class="credit">Tom Reh, Ph.D.</span></div>
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</div><p style="margin-left:0in; margin-right:0in">The retina is the light-sensitive layer of tissue that lines the inside of the eye and sends visual messages through the optic nerve to the brain. Eye injuries and certain eye diseases that damage retinal tissue can lead to blindness. In the mammalian eye, injured retinal cells can’t regenerate.</p>
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<p style="margin-left:0in; margin-right:0in">Retinal cells do naturally regenerate in zebrafish. Müller glia, sometimes referred to as the stem cells of the fish eye, are the cells from which all other types of retinal cells are regenerated in the fish. These cells support the health and functioning of neighboring neurons and have an innate regenerative ability.</p>
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<p style="margin-left:0in; margin-right:0in">A transcription factor called Ascl1 activates a suite of genes involved in regeneration and is present in high amounts after retinal damage in zebrafish. Previous findings have shown that Asc11 can direct Müller glia to become retinal neurons in newborn mice. However, by the time the mice reach adulthood, the regions of the genetic code that are targeted by Ascl1 are no longer accessible.</p>
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<p style="margin-left:0in; margin-right:0in">A team of scientists led by Dr. Tom Reh at UW Medicine in Seattle investigated ways to encourage neuron regeneration in the adult mouse eye. The study was funded in part by NIH’s National Eye Institute (NEI). Results were published in the July 26, 2017, issue of <em>Nature</em>.</p>
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<p style="margin-left:0in; margin-right:0in">The team screened a library of small molecules to find one that could reopen access to the genetic regions targeted by Ascl1 in the adult mouse. They found that an anti-cancer agent called trichostatin A (TSA) altered the DNA to make the regions accessible again. The researchers used adult mice that were genetically engineered to express Ascl1 in Müller glia in response to a drug. A green fluorescent protein gene was inserted next to Ascl1, so that all cells expressing Ascl1 were labeled fluorescent green. The drug turned on Ascl1, and GFP marked the cells where Ascl1 was expressed.</p>
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||
<p style="margin-left:0in; margin-right:0in">After receiving a 5-day treatment to express Ascl1, the genetically engineered mice were injected with a toxin that causes cell death in retinal neurons. They were then given TSA. The team observed the shape and behavior of the fluorescent green-labeled cells for evidence of regeneration over several weeks. Genetic evidence showed that the cells that were once Müller glia were genetically reprogrammed into showing characteristics of interneurons, the cells that transmit signals from photoreceptors to the brain.</p>
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<p style="margin-left:0in; margin-right:0in">The team also found that the cells had formed functioning synapses—connections between neurons—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.</p>
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<p style="margin-left:0in; margin-right:0in">“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,” says Dr. Tom Greenwell, 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.”</p>
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</div><h2 class="label-above">Related Links</h2><ul class="spaced print-urls"><li><a href="https://www.nih.gov/news-events/nih-research-matters/genetic-engineering-prevents-retinal-cell-loss-mice" target="_top">Genetic Engineering Prevents Retinal Cell Loss in Mice</a></li><li><a href="https://www.nih.gov/news-events/nih-research-matters/how-diet-may-affect-age-related-macular-degeneration" target="_top">How Diet May Affect Age-Related Macular Degeneration</a></li><li><a href="https://www.nih.gov/news-events/nih-research-matters/long-term-benefits-age-related-macular-degeneration-treatments" target="_top">Long-Term Benefits of Age-Related Macular Degeneration Treatments</a></li><li><a href="https://www.nih.gov/news-events/nih-research-matters/refining-supplements-blinding-eye-disease" target="_top">Refining Supplements for a Blinding Eye Disease</a></li><li><a href="https://www.nih.gov/news-events/nih-research-matters/genetics-age-related-macular-degeneration" target="_top">The Genetics of Age-Related Macular Degeneration</a></li><li><a href="https://newsinhealth.nih.gov/issue/may2015/feature2" target="_top">Keep Your Vision Healthy: Learn About Comprehensive Dilated Eye Exams</a></li><li><a href="https://newsinhealth.nih.gov/issue/jan2011/feature1" target="_top">Your Aging Eyes: How You See as Time Goes By</a></li><li><a href="https://nei.nih.gov/healthyeyes/aging_eye" target="_top">Age-Related Eye Diseases</a></li></ul><p class="footnote"><strong class="label-inline">References: </strong><a href="https://www.ncbi.nlm.nih.gov/pubmed/28746305">Stimulation of functional neuronal regeneration from Müller glia in adult mice.</a> Jorstad NL, Wilken MS, Grimes WN, Wohl SG, VandenBosch LS, Yoshimatsu T, Wong RO, Rieke F, Reh TA. <em>Nature</em>. 2017 Jul 26. doi: 10.1038/nature23283. [Epub ahead of print] PMID: 28746305.</p><p class="footnote"><strong class="label-inline">Funding: </strong>National Institutes of Health’s National Eye Institute (NEI) and National Institute of General Medical Sciences (NIGMS); Howard Hughes Medical Institute; Paul G. Allen Family Foundation; and National Science Foundation.</p>
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<p><strong>Mailing Address:</strong><br />
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NIH Research Matters<br />
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Bldg. 31, Rm. 5B52, MSC 2094<br />
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<p><a href="https://www.nih.gov/news-events/nih-research-matters/research-context-can-we-slow-aging">Research in Context: Can we slow aging?</a></p>
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<p><a href="https://www.nih.gov/news-events/nih-research-matters/brain-changes-observed-during-pregnancy">Brain changes observed during pregnancy</a></p>
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<p><a href="https://www.nih.gov/news-events/nih-research-matters/research-context-detecting-cancer">Research in Context: Detecting cancer</a></p>
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<p><a href="https://www.nih.gov/news-events/nih-research-matters/risk-future-burden-dementia-united-states">Risk and future burden of dementia in the United States </a></p>
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<p><a href="https://www.nih.gov/news-events/nih-research-matters/complete-wiring-map-adult-fruit-fly-brain">Complete wiring map of an adult fruit fly brain</a></p>
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<p><strong>Editor:</strong> Harrison Wein, Ph.D.</p>
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<p><strong>Assistant Editors:</strong> Vicki Contie and Brian Doctrow, Ph.D.</p>
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<p><strong><em>NIH Research Matters </em></strong>is a weekly update of NIH research highlights reviewed by NIH’s experts. It's published by the <a href="/institutes-nih/nih-office-director/office-communications-public-liaison">Office of Communications and Public Liaison</a> in the <a href="/institutes-nih/nih-office-director">NIH Office of the Director</a>.</p>
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