7/21/2021
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`Researchers uncover mechanism blocking retina regeneration | EurekAlert! Science News
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`NEWS RELEASE 7-MAY-2019
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`Researchers uncover mechanism blocking
`retina regeneration
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`BAYLOR COLLEGE OF MEDICINE
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`MAGE: DR. ROSS A. POCHE view more 
`CREDIT: BAYLOR COLLEGE OF MEDICINE
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`A discovery opens the possibility of one day restoring loss of vision by activating the retina's ability to
`regenerate. Researchers at Baylor College of Medicine, the Cardiovascular Research Institute and the Texas
`eart Institute reveal in the journal Cell Reports that although the mammalian retina a layer of specialized
`nerve cells that mediates vision and is located on the back of the eye- does not spontaneously regenerate, it
`has a regenerative capacity that is kept dormant by a cellular mechanism called the Hippo pathway. The
`discovery opens the possibility of activating the retina's ability to restore lost vision by manipulating this
`pathway
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`"Damage to the retina can lead to irreparable loss of vision in humans and other mammals because their
`retinas do not regenerate," said lead author Dr. Ross A. Poché, assistant professor of molecular physiology
`and biophysics and member of the Dan L Duncan Comprehensive Cancer Center at Baylor "However, other
`animals such as zebrash can reverse blindness thanks to specialized cells in the retina cal ed Müller glial cells.
`When the retina is damaged, Müller glial cells proliferate and dierentiate into the lost retinal neurons,
`eectively replacing injured cells with fully functional ones."
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`Although Müller glial cells in injured mammalian retina do not restore vision as their counterpart in zebrash
`do, other researchers have shown that, when the mammalian retina is injured, a small subset of Müller glial
`cells takes the rst steps needed to enter the proliferation cycle, such as acquiring molecular markers
`scientists expect to see in a proliferating cell
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`https://www.eurekalert.org/pub_releases/2019-05/bcom-rum050619.php
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`Researchers uncover mechanism blocking retina regeneration | EurekAlert! Science News
`7/21/2021
`"But this attempt to proliferate is transient; after acquiring some of the cell markers the cells shut o," said
`Poché, who also is aliated with the Intellectual and Developmental Disabilities Research Center and the
`Cullen Eye Institute, both at Baylor. "These observations suggested that the mechanism that drives cell repair
`n zebrash also might be present in mammals, but it is actively suppressed For years, the suppressing
`mechanism was unknown."
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`Searching for the proposed suppressing mechanism, the Poché lab combined forces with the lab of co-
`orresponding author Dr James Martin, professor of molecular physiology and biophysics, Vivian L Smith
`Chair in Regenerative Medicine at Baylor College of Medicine and director of the Cardiomyocyte Renewal Lab
`at the Texas Heart Institute. The researchers focused their attention on the Hippo pathway, a network of
`molecular events that contributes to organ growth during development and to the regulation of heart tissue
`egeneration in response to myocardial infarction The Martin lab previously showed that the Hippo pathway
`acts like a 'break' on cardiomyocyte proliferation by inhibiting the activity of another pathway called YAP.
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`n this study, the researchers rst determined that the Hippo pathway is expressed in mammalian Müller glial
`ells Then, they investigated whether altering the Hippo pathway in these cells would aect their ability to
`proliferate. Creating a malfunctioning Hippo pathway by eliminating two of its molecular steps resulted in
`modest cell proliferation. And when the researchers genetically engineered Müller glial cells to carry a version
`of YAP called YAP5SA that is impervious to the inhibitory inuence of Hippo, the cells showed major
`proliferation and acquired a progenitor cell identity Importantly, a small subset of these Müller glia derived
`progenitor cells showed signs of spontaneous dierentiation into new retinal neurons.
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`"Up to this point researchers did not know what endogenous blocking mechanism prevented Müller cells from
`entering a regenerative state The Hippo pathway is a new molecular entry point to that mechanism," said
`Poché. "Our next step is to develop a strategy to guide proliferating Müller glial cells into dierentiation
`pathways leading to retinal cells capable of restoring vision."
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`###
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`Other contributors to this work include Elda M. Rueda, Benjamin M. Hall, Matthew C. Hill, Paul G. Swinton and
`Xuefei Tong. The authors are aliated with one or more of the following institutions: Baylor College of
`Medicine, the Cardiovascular Research Institute and the Texas Heart Institute
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`This work was supported by National Institutes of Health grants P30 AI036211, P30 CA125123, S10 RR024574,
`U543 HG006348, R01 EY024906, R01 DE023177, R01 HL127717, R01 HL118761, R01 HL130804 and F31
`L136065 Additional support was provided by the Vivian L Smith Foundation, MacDonald Research Fund
`award 16RDM001 and the Bright Focus Foundation Macular Degeneration Research Grant.
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`7/21/2021
`Graciela Gutierrez
`ggutierr@bcm.edu
`13 798 4710
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`Researchers uncover mechanism blocking retina regeneration | EurekAlert! Science News
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