Epigenetic regulation of αA-crystallin in high myopia-induced dark nuclear cataract
To assess the etiology of early-onset dark nucleus in high-myopic patients and its relationship with the epigenetic regulation of αA-crystallin (CRYAA). We reviewed clinical data from patients who underwent cataract surgery at our center in 2012. Lens epithelial samples were collected during capsulo...
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description | To assess the etiology of early-onset dark nucleus in high-myopic patients and its relationship with the epigenetic regulation of αA-crystallin (CRYAA).
We reviewed clinical data from patients who underwent cataract surgery at our center in 2012. Lens epithelial samples were collected during capsulorhexis, whereas young lens epithelium was donated. Cataract type and severity were graded according to the Lens Opacity Classification System III (LOCS III). DNA methylation was analyzed by pyrosequencing the CpG islands of the CRYAA promoter in the following groups: Age-Related Cataract (ARC) Nuclear Color (NC) 2-3; High-Myopic Cataract (HMC) NC2-3; ARC NC5-6; HMC NC5-6; and in young lenses graded NC1. We analyzed CRYAA expression by real-time polymerase chain reaction (PCR), reverse transcription PCR, and immunohistochemistry.
The odds ratio of dark nucleus in high-myopic patients was 5.16 (95% confidence interval: 3.98-6.69; p |
doi_str_mv | 10.1371/journal.pone.0081900 |
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We reviewed clinical data from patients who underwent cataract surgery at our center in 2012. Lens epithelial samples were collected during capsulorhexis, whereas young lens epithelium was donated. Cataract type and severity were graded according to the Lens Opacity Classification System III (LOCS III). DNA methylation was analyzed by pyrosequencing the CpG islands of the CRYAA promoter in the following groups: Age-Related Cataract (ARC) Nuclear Color (NC) 2-3; High-Myopic Cataract (HMC) NC2-3; ARC NC5-6; HMC NC5-6; and in young lenses graded NC1. We analyzed CRYAA expression by real-time polymerase chain reaction (PCR), reverse transcription PCR, and immunohistochemistry.
The odds ratio of dark nucleus in high-myopic patients was 5.16 (95% confidence interval: 3.98-6.69; p<0.001). CpG islands in lens epithelial CRYAA promoter in the HMC NC5-6 Group exhibited the highest methylation of all the groups, but no statistically significant differences were evident between the HMC NC2-3 and ARC NC2-3 Groups. Likewise, CRYAA mRNA and protein levels in the HMC NC5-6 Group were significantly lower than the ARC NC5-6 Group and high-myopic controls.
High myopia is a risk factor for dark nucleus. Downregulation of CRYAA via the hypermethylation of CpG islands in its promoter could underlie the earlier onset of dark nucleus in high-myopic patients.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0081900</identifier><identifier>PMID: 24312600</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adult ; Age ; Aged ; alpha-Crystallin A Chain - genetics ; Apoptosis ; Boscia ; Cataract - etiology ; Cataract - genetics ; Cataracts ; Confidence intervals ; CpG islands ; CpG Islands - genetics ; Crystal structure ; Crystallin ; Crystallinity ; Deoxyribonucleic acid ; Diabetes ; DNA ; DNA Methylation ; Epigenesis, Genetic ; Epigenetics ; Epithelium ; Epithelium - metabolism ; Etiology ; Eye surgery ; Female ; Gene expression ; Glaucoma ; Humans ; Immunohistochemistry ; Islands ; Lens, Crystalline - metabolism ; Lenses ; Male ; Middle Aged ; Myopia ; Myopia - complications ; Nuclei ; Opacity ; Patients ; Polymerase chain reaction ; Promoter Regions, Genetic - genetics ; Proteins ; Reverse transcription ; Risk Factors ; Statistical analysis ; Statistical methods ; Studies ; Surgery</subject><ispartof>PloS one, 2013-12, Vol.8 (12), p.e81900-e81900</ispartof><rights>2013 Zhu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/3.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2013 Zhu et al 2013 Zhu et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c526t-b18b23f1deca7af16f561d39c63297ab2a3269a34e0646ab174c0425185eaf213</citedby><cites>FETCH-LOGICAL-c526t-b18b23f1deca7af16f561d39c63297ab2a3269a34e0646ab174c0425185eaf213</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3849391/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3849391/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24312600$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhu, Xiang-Jia</creatorcontrib><creatorcontrib>Zhou, Peng</creatorcontrib><creatorcontrib>Zhang, Ke-Ke</creatorcontrib><creatorcontrib>Yang, Jin</creatorcontrib><creatorcontrib>Luo, Yi</creatorcontrib><creatorcontrib>Lu, Yi</creatorcontrib><title>Epigenetic regulation of αA-crystallin in high myopia-induced dark nuclear cataract</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>To assess the etiology of early-onset dark nucleus in high-myopic patients and its relationship with the epigenetic regulation of αA-crystallin (CRYAA).
We reviewed clinical data from patients who underwent cataract surgery at our center in 2012. Lens epithelial samples were collected during capsulorhexis, whereas young lens epithelium was donated. Cataract type and severity were graded according to the Lens Opacity Classification System III (LOCS III). DNA methylation was analyzed by pyrosequencing the CpG islands of the CRYAA promoter in the following groups: Age-Related Cataract (ARC) Nuclear Color (NC) 2-3; High-Myopic Cataract (HMC) NC2-3; ARC NC5-6; HMC NC5-6; and in young lenses graded NC1. We analyzed CRYAA expression by real-time polymerase chain reaction (PCR), reverse transcription PCR, and immunohistochemistry.
The odds ratio of dark nucleus in high-myopic patients was 5.16 (95% confidence interval: 3.98-6.69; p<0.001). CpG islands in lens epithelial CRYAA promoter in the HMC NC5-6 Group exhibited the highest methylation of all the groups, but no statistically significant differences were evident between the HMC NC2-3 and ARC NC2-3 Groups. Likewise, CRYAA mRNA and protein levels in the HMC NC5-6 Group were significantly lower than the ARC NC5-6 Group and high-myopic controls.
High myopia is a risk factor for dark nucleus. Downregulation of CRYAA via the hypermethylation of CpG islands in its promoter could underlie the earlier onset of dark nucleus in high-myopic patients.</description><subject>Adult</subject><subject>Age</subject><subject>Aged</subject><subject>alpha-Crystallin A Chain - genetics</subject><subject>Apoptosis</subject><subject>Boscia</subject><subject>Cataract - etiology</subject><subject>Cataract - genetics</subject><subject>Cataracts</subject><subject>Confidence intervals</subject><subject>CpG islands</subject><subject>CpG Islands - genetics</subject><subject>Crystal structure</subject><subject>Crystallin</subject><subject>Crystallinity</subject><subject>Deoxyribonucleic acid</subject><subject>Diabetes</subject><subject>DNA</subject><subject>DNA Methylation</subject><subject>Epigenesis, Genetic</subject><subject>Epigenetics</subject><subject>Epithelium</subject><subject>Epithelium - metabolism</subject><subject>Etiology</subject><subject>Eye surgery</subject><subject>Female</subject><subject>Gene expression</subject><subject>Glaucoma</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Islands</subject><subject>Lens, Crystalline - metabolism</subject><subject>Lenses</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Myopia</subject><subject>Myopia - complications</subject><subject>Nuclei</subject><subject>Opacity</subject><subject>Patients</subject><subject>Polymerase chain reaction</subject><subject>Promoter Regions, Genetic - genetics</subject><subject>Proteins</subject><subject>Reverse transcription</subject><subject>Risk Factors</subject><subject>Statistical analysis</subject><subject>Statistical methods</subject><subject>Studies</subject><subject>Surgery</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNptUs1q3DAYNKEhSdO-QWkNvfTirf5tXQohpG0gkEt6Fp8l2autVnIlO7CP1RfpM9WbdUJSCgIJaWY08zFF8Q6jFaY1_ryJUwrgV0MMdoVQgyVCR8UZlpRUgiD66tn5tHid8wYhThshTopTwigmAqGz4u5qcL0NdnS6TLafPIwuhjJ25Z_fF5VOuzyC9y6U81q7fl1ud3FwULlgJm1NaSD9LMOkvYVUahghgR7fFMcd-GzfLvt58ePr1d3l9-rm9tv15cVNpTkRY9XipiW0w8ZqqKHDouMCGyq1oETW0BKgREigzCLBBLS4ZhoxwnHDLXQE0_Piw0F38DGrZSBZYTbDCZ2nNCOuDwgTYaOG5LaQdiqCUw8XMfUK0pzdW8UlpwY1spaEMd2IBslOdrTlhmPUGjFrfVl-m9qtNdqGMYF_IfryJbi16uO9og2TVO7tfloEUvw12Tyqrcvaeg_BxunBN28En9PP0I__QP-fjh1QOsWck-2ezGCk9iV5ZKl9SdRSkpn2_nmQJ9JjK-hfKw26lA</recordid><startdate>20131203</startdate><enddate>20131203</enddate><creator>Zhu, Xiang-Jia</creator><creator>Zhou, Peng</creator><creator>Zhang, Ke-Ke</creator><creator>Yang, Jin</creator><creator>Luo, Yi</creator><creator>Lu, Yi</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20131203</creationdate><title>Epigenetic regulation of αA-crystallin in high myopia-induced dark nuclear cataract</title><author>Zhu, Xiang-Jia ; Zhou, Peng ; Zhang, Ke-Ke ; Yang, Jin ; Luo, Yi ; Lu, Yi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c526t-b18b23f1deca7af16f561d39c63297ab2a3269a34e0646ab174c0425185eaf213</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Adult</topic><topic>Age</topic><topic>Aged</topic><topic>alpha-Crystallin A Chain - genetics</topic><topic>Apoptosis</topic><topic>Boscia</topic><topic>Cataract - etiology</topic><topic>Cataract - genetics</topic><topic>Cataracts</topic><topic>Confidence intervals</topic><topic>CpG islands</topic><topic>CpG Islands - genetics</topic><topic>Crystal structure</topic><topic>Crystallin</topic><topic>Crystallinity</topic><topic>Deoxyribonucleic acid</topic><topic>Diabetes</topic><topic>DNA</topic><topic>DNA Methylation</topic><topic>Epigenesis, Genetic</topic><topic>Epigenetics</topic><topic>Epithelium</topic><topic>Epithelium - metabolism</topic><topic>Etiology</topic><topic>Eye surgery</topic><topic>Female</topic><topic>Gene expression</topic><topic>Glaucoma</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Islands</topic><topic>Lens, Crystalline - metabolism</topic><topic>Lenses</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Myopia</topic><topic>Myopia - complications</topic><topic>Nuclei</topic><topic>Opacity</topic><topic>Patients</topic><topic>Polymerase chain reaction</topic><topic>Promoter Regions, Genetic - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhu, Xiang-Jia</au><au>Zhou, Peng</au><au>Zhang, Ke-Ke</au><au>Yang, Jin</au><au>Luo, Yi</au><au>Lu, Yi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Epigenetic regulation of αA-crystallin in high myopia-induced dark nuclear cataract</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2013-12-03</date><risdate>2013</risdate><volume>8</volume><issue>12</issue><spage>e81900</spage><epage>e81900</epage><pages>e81900-e81900</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>To assess the etiology of early-onset dark nucleus in high-myopic patients and its relationship with the epigenetic regulation of αA-crystallin (CRYAA).
We reviewed clinical data from patients who underwent cataract surgery at our center in 2012. Lens epithelial samples were collected during capsulorhexis, whereas young lens epithelium was donated. Cataract type and severity were graded according to the Lens Opacity Classification System III (LOCS III). DNA methylation was analyzed by pyrosequencing the CpG islands of the CRYAA promoter in the following groups: Age-Related Cataract (ARC) Nuclear Color (NC) 2-3; High-Myopic Cataract (HMC) NC2-3; ARC NC5-6; HMC NC5-6; and in young lenses graded NC1. We analyzed CRYAA expression by real-time polymerase chain reaction (PCR), reverse transcription PCR, and immunohistochemistry.
The odds ratio of dark nucleus in high-myopic patients was 5.16 (95% confidence interval: 3.98-6.69; p<0.001). CpG islands in lens epithelial CRYAA promoter in the HMC NC5-6 Group exhibited the highest methylation of all the groups, but no statistically significant differences were evident between the HMC NC2-3 and ARC NC2-3 Groups. Likewise, CRYAA mRNA and protein levels in the HMC NC5-6 Group were significantly lower than the ARC NC5-6 Group and high-myopic controls.
High myopia is a risk factor for dark nucleus. Downregulation of CRYAA via the hypermethylation of CpG islands in its promoter could underlie the earlier onset of dark nucleus in high-myopic patients.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24312600</pmid><doi>10.1371/journal.pone.0081900</doi><oa>free_for_read</oa></addata></record> |
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subjects | Adult Age Aged alpha-Crystallin A Chain - genetics Apoptosis Boscia Cataract - etiology Cataract - genetics Cataracts Confidence intervals CpG islands CpG Islands - genetics Crystal structure Crystallin Crystallinity Deoxyribonucleic acid Diabetes DNA DNA Methylation Epigenesis, Genetic Epigenetics Epithelium Epithelium - metabolism Etiology Eye surgery Female Gene expression Glaucoma Humans Immunohistochemistry Islands Lens, Crystalline - metabolism Lenses Male Middle Aged Myopia Myopia - complications Nuclei Opacity Patients Polymerase chain reaction Promoter Regions, Genetic - genetics Proteins Reverse transcription Risk Factors Statistical analysis Statistical methods Studies Surgery |
title | Epigenetic regulation of αA-crystallin in high myopia-induced dark nuclear cataract |
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