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<p class="publishdate"><span property="dc:date" datatype="xsd:dateTime" content="2024-10-01T00:00:00-04:00" class="date-display-single">October 1, 2024</span></p><div class='syndicate'><h1>Potential target for cataract drug development</h1><div class="callout callout-with-border"><h3>At a Glance</h3>
<ul>
<li>Researchers discovered a protein produced by hibernating ground squirrels that allows their eyes to rapidly clear cataracts formed during cold exposure.</li>
<li>The eyes of rats and fish treated with this protein gained the ability to clear cataracts, suggesting a potential drug treatment strategy.</li>
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<picture title="Close-up of 13-lined ground squirrel.">
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-large/public/news-events/research-matters/2024/20241001-squirrel.jpeg?itok=ODg6SePx&amp;timestamp=1727793800 1x" media="screen and (min-width: 960px)" />
<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium/public/news-events/research-matters/2024/20241001-squirrel.jpeg?itok=u_rGrFFQ&amp;timestamp=1727793800 1x" media="screen and (min-width: 800px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-tiny/public/news-events/research-matters/2024/20241001-squirrel.jpeg?itok=SdeFYRfQ&amp;timestamp=1727793800 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/2024/20241001-squirrel.jpeg?itok=u_rGrFFQ&amp;timestamp=1727793800" alt="Close-up of 13-lined ground squirrel." title="Close-up of 13-lined ground squirrel." />
</picture><span class="caption">The 13-lined ground squirrel is a good model system for studying cataracts because cataracts form in the squirrels during hibernation but then disappear when their body temperature returns to normal. </span><span class="credit">sdbower / Adobe Stock</span></div>
</div><p>Cataracts are a common cause of vision loss in older adults. They occur when proteins in the eyes lens become damaged and begin to clump together. This can lead to cloudy or blurry vision, or other problems with sight.</p>
<p>Currently, the only available treatment for cataracts is surgery to remove and replace the clouded lens. But while effective, such surgery comes with risks. Its also not readily available in many parts of the world.</p>
<p>To better understand cataracts, an international research team including NIH investigators has been studying the 13-lined ground squirrel. These squirrels hibernate during the winter. During hibernation, their body temperature drops to around 4 degrees Celsius (39 degrees Fahrenheit). Cataracts form in the squirrels eyes during this extended cold period. But when their body temperature returns to normal, the cataracts disappear. Understanding how the squirrel eye clears cataracts could lead to new treatments in people.</p>
<p>To examine this process at the molecular level, the researchers studied eye lenses from squirrels and from rats. They also developed a method to grow stem cells from squirrels into the main type of cell found within the lens. Results from their new experiments were published on September 17, 2024, in the <em>Journal of Clinical Investigation</em>.</p>
<p>As expected, squirrel lenses cooled to 4 degrees Celsius for 24 hours became clouded by cataracts. But the cloudiness disappeared within about 5 minutes of warming to normal body temperature. In contrast, rat lenses exposed to the same cooling regimen remained partially cloudy.</p>
<p>Analysis of eye lens tissue found that rewarming triggered a process in squirrel eyes called ubiquitination. This process breaks down damaged or misfolded proteins so they can be replaced by healthy new ones. In contrast, rewarming in rat eyes resulted in higher activation of chaperone proteins. These kinds of proteins can help refold some damaged proteins, but they cant break them down for replacement.</p>
<p>In experiments with their stem cell-derived eye cells, the researchers identified a protein involved in ubiquitination, called RNF114, that appeared to trigger the rapid breakdown of CRYAA, an eye lens protein associated with cataracts. When the team engineered human eye cells to produce RNF114, they also gained the ability to break down clumps of CRYAA.</p>
<p>To see if RNF114 had the potential to be delivered as a drug, the researchers attached it to a small molecule that enabled it to enter cells. When the team added the RNF114 to rat eye lenses before cold exposure, the resulting cataracts cleared rapidly after rewarming. Similar results were seen with zebrafish eyes that developed cataracts after exposure to hydrogen peroxide.</p>
<p>“Understanding the molecular drivers of this reversible cataract phenomenon might point us in a direction toward a potential treatment strategy,” says Dr. Wei Li from NIHs National Eye Institute, who helped lead the study.</p>
<p>The findings suggest a possible surgery-free approach for managing cataracts. More work will be needed before this strategy could be tested in people.</p></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/liquid-biopsies-ai-give-insight-into-eye-health-aging" target="_top">Liquid Biopsies and AI Give Insight into Eye Health and Aging</a></li><li><a href="https://newsinhealth.nih.gov/2022/09/cloudy-vision" target="_top">Cloudy Vision? It Could Be Cataracts</a></li><li><a href="https://newsinhealth.nih.gov/2018/05/keep-eye-your-eyes" target="_top">Keep an Eye on Your Eyes: Technologies For Protecting Vision</a></li><li><a href="https://www.nei.nih.gov/learn-about-eye-health/eye-conditions-and-diseases/cataracts" target="_top">Cataracts</a></li></ul><p class="footnote"><strong class="label-inline">References:&nbsp;</strong><a href="https://pubmed.ncbi.nlm.nih.gov/39286982/">Reversible cold-induced lens opacity in a hibernator reveals a molecular target for treating cataracts.</a> Yang H, Ping X, Zhou J, Ailifeire H, Wu J, Nadal-Nicolás FM, Miyagishima KJ, Bao J, Huang Y, Cui Y, Xing X, Wang S, Yao K, Li W, Shentu X. <em>J Clin Invest</em>. 2024 Sep 17;134(18):e169666. doi: 10.1172/JCI169666. PMID: 39286982.</p><p class="footnote"><strong class="label-inline">Funding:&nbsp;</strong>NIHs National Eye Institute (NEI); National Natural Science Foundation of China; Natural Science Foundation of Zhejiang Province; Zhejiang Medical and Health Science and Technology Plan Project; Zhejiang Traditional Chinese Medicine Science and Technology Project.</p>
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