OFD1, as a Ciliary Protein, Exhibits Neuroprotective Function in Photoreceptor Degeneration Models
Ofd1 is a newly identified causative gene for Retinitis pigmentosa (RP), a photoreceptor degenerative disease. This study aimed to examine Ofd1 localization in retina and further to investigate its function in photoreceptor degeneration models. Ofd1 localization in rat retina was examined using immu...
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| Veröffentlicht in: | PloS one 2016-05, Vol.11 (5), p.e0155860 |
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| creator | Wang, Juan Chen, Xin Wang, Fang Zhang, Jieping Li, Peng Li, Zongyi Xu, Jingying Gao, Furong Jin, Caixia Tian, Haibin Zhang, Jingfa Li, Weiye Lu, Lixia Xu, Guo-Tong |
| description | Ofd1 is a newly identified causative gene for Retinitis pigmentosa (RP), a photoreceptor degenerative disease. This study aimed to examine Ofd1 localization in retina and further to investigate its function in photoreceptor degeneration models. Ofd1 localization in rat retina was examined using immunofluorescence. N-methyl-N-nitrosourea (MNU)-induced rats and Royal College of Surgeons (RCS) rats were used as photoreceptor degeneration models. The expression pattern of Ofd1, other ciliary associated genes and Wnt signaling pathway genes were examined in rat models. Furthermore, pEGFP-Ofd1-CDS and pSUPER-Ofd1-shRNA were constructed to overexpress and knockdown the expression level in 661W and R28 cells. MNU was also used to induce cell death. Cilia formation was observed using immunocytochemistry (ICC). Reactive oxygen species (ROS) were detected using the 2', 7'-Dichlorofluorescin diacetate (DCFH-DA) assay. Apoptosis genes expression was examined using qRT-PCR, Western blotting and fluorescence-activated cell sorting (FACS). Ofd1 localized to outer segments of rat retina photoreceptors. Ofd1 and other ciliary proteins expression levels increased from the 1st and 4th postnatal weeks and decreased until the 6th week in the RCS rats, while their expression consistently decreased from the 1st and 7th day in the MNU rats. Moreover, Wnt signaling pathway proteins expression was significantly up-regulated in both rat models. Knockdown of Ofd1 expression resulted in a smaller population, shorter length of cell cilia, and lower cell viability. Ofd1 overexpression partially attenuated MNU toxic effects by reducing ROS levels and mitigating apoptosis. To the best of our knowledge, this is the first study demonstrating Ofd1 localization and its function in rat retina and in retinal degeneration rat models. Ofd1 plays a role in controlling photoreceptor cilium length and number. Importantly, it demonstrates a neuroprotective function by protecting the photoreceptor from oxidative stress and apoptosis. These data have expanded our understanding of Ofd1 function beyond cilia, and we concluded that ofd1 neuroprotection could be a potential treatment strategy in retina degeneration models. |
| doi_str_mv | 10.1371/journal.pone.0155860 |
| format | Article |
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This study aimed to examine Ofd1 localization in retina and further to investigate its function in photoreceptor degeneration models. Ofd1 localization in rat retina was examined using immunofluorescence. N-methyl-N-nitrosourea (MNU)-induced rats and Royal College of Surgeons (RCS) rats were used as photoreceptor degeneration models. The expression pattern of Ofd1, other ciliary associated genes and Wnt signaling pathway genes were examined in rat models. Furthermore, pEGFP-Ofd1-CDS and pSUPER-Ofd1-shRNA were constructed to overexpress and knockdown the expression level in 661W and R28 cells. MNU was also used to induce cell death. Cilia formation was observed using immunocytochemistry (ICC). Reactive oxygen species (ROS) were detected using the 2', 7'-Dichlorofluorescin diacetate (DCFH-DA) assay. Apoptosis genes expression was examined using qRT-PCR, Western blotting and fluorescence-activated cell sorting (FACS). Ofd1 localized to outer segments of rat retina photoreceptors. Ofd1 and other ciliary proteins expression levels increased from the 1st and 4th postnatal weeks and decreased until the 6th week in the RCS rats, while their expression consistently decreased from the 1st and 7th day in the MNU rats. Moreover, Wnt signaling pathway proteins expression was significantly up-regulated in both rat models. Knockdown of Ofd1 expression resulted in a smaller population, shorter length of cell cilia, and lower cell viability. Ofd1 overexpression partially attenuated MNU toxic effects by reducing ROS levels and mitigating apoptosis. To the best of our knowledge, this is the first study demonstrating Ofd1 localization and its function in rat retina and in retinal degeneration rat models. Ofd1 plays a role in controlling photoreceptor cilium length and number. Importantly, it demonstrates a neuroprotective function by protecting the photoreceptor from oxidative stress and apoptosis. These data have expanded our understanding of Ofd1 function beyond cilia, and we concluded that ofd1 neuroprotection could be a potential treatment strategy in retina degeneration models.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0155860</identifier><identifier>PMID: 27196396</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animal models ; Animals ; Antioxidants - metabolism ; Apoptosis ; Biology and Life Sciences ; Cell Death ; Cell Line ; Cell Separation ; Cilia ; Cilia - metabolism ; Ciliopathies ; Congenital diseases ; Degeneration ; Development and progression ; Disease ; Electroretinography ; Flow Cytometry ; Fluorescence ; Gene expression ; Genes ; Genetic aspects ; Hospitals ; Immunocytochemistry ; Immunofluorescence ; Immunohistochemistry ; Localization ; Medical personnel ; Medical research ; Medicine ; Medicine and Health Sciences ; Methylnitrosourea - pharmacology ; Mice ; Multiple abnormalities ; Mutation ; N-Methyl-N-nitrosourea ; Neuroprotection ; Oxidative Stress ; Oxygen ; Photoreceptor Cells - pathology ; Photoreceptor Cells, Vertebrate - metabolism ; Photoreceptors ; Physiological aspects ; Plasmids - metabolism ; Proteins ; Proteins - genetics ; Rats ; Reactive oxygen species ; Reactive Oxygen Species - metabolism ; Retina ; Retina - metabolism ; Retina - pathology ; Retinal degeneration ; Retinal Degeneration - metabolism ; Retinal Degeneration - pathology ; Retinitis ; Retinitis pigmentosa ; Retinitis Pigmentosa - genetics ; Retinitis Pigmentosa - metabolism ; Risk factors ; RNA, Small Interfering - metabolism ; Satellites ; Signal Transduction ; Signaling ; Social Sciences ; Stem cells ; Stem Cells - cytology ; Therapeutic applications ; Toxicity ; Western blotting ; Wnt protein</subject><ispartof>PloS one, 2016-05, Vol.11 (5), p.e0155860</ispartof><rights>COPYRIGHT 2016 Public Library of Science</rights><rights>2016 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (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>2016 Wang et al 2016 Wang et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-83de3908123bb8587cf5bbd93201431770aa3298a6787b474565290b6d6026803</citedby><cites>FETCH-LOGICAL-c758t-83de3908123bb8587cf5bbd93201431770aa3298a6787b474565290b6d6026803</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/PMC4873209/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4873209/$$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/27196396$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Juan</creatorcontrib><creatorcontrib>Chen, Xin</creatorcontrib><creatorcontrib>Wang, Fang</creatorcontrib><creatorcontrib>Zhang, Jieping</creatorcontrib><creatorcontrib>Li, Peng</creatorcontrib><creatorcontrib>Li, Zongyi</creatorcontrib><creatorcontrib>Xu, Jingying</creatorcontrib><creatorcontrib>Gao, Furong</creatorcontrib><creatorcontrib>Jin, Caixia</creatorcontrib><creatorcontrib>Tian, Haibin</creatorcontrib><creatorcontrib>Zhang, Jingfa</creatorcontrib><creatorcontrib>Li, Weiye</creatorcontrib><creatorcontrib>Lu, Lixia</creatorcontrib><creatorcontrib>Xu, Guo-Tong</creatorcontrib><title>OFD1, as a Ciliary Protein, Exhibits Neuroprotective Function in Photoreceptor Degeneration Models</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Ofd1 is a newly identified causative gene for Retinitis pigmentosa (RP), a photoreceptor degenerative disease. This study aimed to examine Ofd1 localization in retina and further to investigate its function in photoreceptor degeneration models. Ofd1 localization in rat retina was examined using immunofluorescence. N-methyl-N-nitrosourea (MNU)-induced rats and Royal College of Surgeons (RCS) rats were used as photoreceptor degeneration models. The expression pattern of Ofd1, other ciliary associated genes and Wnt signaling pathway genes were examined in rat models. Furthermore, pEGFP-Ofd1-CDS and pSUPER-Ofd1-shRNA were constructed to overexpress and knockdown the expression level in 661W and R28 cells. MNU was also used to induce cell death. Cilia formation was observed using immunocytochemistry (ICC). Reactive oxygen species (ROS) were detected using the 2', 7'-Dichlorofluorescin diacetate (DCFH-DA) assay. Apoptosis genes expression was examined using qRT-PCR, Western blotting and fluorescence-activated cell sorting (FACS). Ofd1 localized to outer segments of rat retina photoreceptors. Ofd1 and other ciliary proteins expression levels increased from the 1st and 4th postnatal weeks and decreased until the 6th week in the RCS rats, while their expression consistently decreased from the 1st and 7th day in the MNU rats. Moreover, Wnt signaling pathway proteins expression was significantly up-regulated in both rat models. Knockdown of Ofd1 expression resulted in a smaller population, shorter length of cell cilia, and lower cell viability. Ofd1 overexpression partially attenuated MNU toxic effects by reducing ROS levels and mitigating apoptosis. To the best of our knowledge, this is the first study demonstrating Ofd1 localization and its function in rat retina and in retinal degeneration rat models. Ofd1 plays a role in controlling photoreceptor cilium length and number. Importantly, it demonstrates a neuroprotective function by protecting the photoreceptor from oxidative stress and apoptosis. These data have expanded our understanding of Ofd1 function beyond cilia, and we concluded that ofd1 neuroprotection could be a potential treatment strategy in retina degeneration models.</description><subject>Animal models</subject><subject>Animals</subject><subject>Antioxidants - metabolism</subject><subject>Apoptosis</subject><subject>Biology and Life Sciences</subject><subject>Cell Death</subject><subject>Cell Line</subject><subject>Cell Separation</subject><subject>Cilia</subject><subject>Cilia - metabolism</subject><subject>Ciliopathies</subject><subject>Congenital diseases</subject><subject>Degeneration</subject><subject>Development and progression</subject><subject>Disease</subject><subject>Electroretinography</subject><subject>Flow Cytometry</subject><subject>Fluorescence</subject><subject>Gene expression</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Hospitals</subject><subject>Immunocytochemistry</subject><subject>Immunofluorescence</subject><subject>Immunohistochemistry</subject><subject>Localization</subject><subject>Medical personnel</subject><subject>Medical research</subject><subject>Medicine</subject><subject>Medicine and Health Sciences</subject><subject>Methylnitrosourea - pharmacology</subject><subject>Mice</subject><subject>Multiple abnormalities</subject><subject>Mutation</subject><subject>N-Methyl-N-nitrosourea</subject><subject>Neuroprotection</subject><subject>Oxidative Stress</subject><subject>Oxygen</subject><subject>Photoreceptor Cells - pathology</subject><subject>Photoreceptor Cells, Vertebrate - metabolism</subject><subject>Photoreceptors</subject><subject>Physiological aspects</subject><subject>Plasmids - metabolism</subject><subject>Proteins</subject><subject>Proteins - genetics</subject><subject>Rats</subject><subject>Reactive oxygen species</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>Retina</subject><subject>Retina - metabolism</subject><subject>Retina - pathology</subject><subject>Retinal degeneration</subject><subject>Retinal Degeneration - metabolism</subject><subject>Retinal Degeneration - pathology</subject><subject>Retinitis</subject><subject>Retinitis pigmentosa</subject><subject>Retinitis Pigmentosa - genetics</subject><subject>Retinitis Pigmentosa - metabolism</subject><subject>Risk factors</subject><subject>RNA, Small Interfering - metabolism</subject><subject>Satellites</subject><subject>Signal Transduction</subject><subject>Signaling</subject><subject>Social Sciences</subject><subject>Stem cells</subject><subject>Stem Cells - cytology</subject><subject>Therapeutic applications</subject><subject>Toxicity</subject><subject>Western blotting</subject><subject>Wnt protein</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNkl1r2zAYhc3YWD-2fzA2wWAwaDLJsj58MyhpswW6pezrVsiy7Cg4lifJpf33kxu3xLDB0IXEq-c90ns4SfIKwTnCDH3Y2t61spl3ttVziAjhFD5JjlGO0xlNIX56cD5KTrzfQkgwp_R5cpQylFOc0-OkWC8v0BmQHkiwMI2R7g5cOxu0ac_A5e3GFCZ48FX3znZDWQVzo8Gyb-PBtsC04Hpjg3Va6S5u4ELXutVO3t9-saVu_IvkWSUbr1-O-2nyc3n5Y_F5drX-tFqcX80UIzzMOC41ziFHKS4KTjhTFSmKMo4AUYYRY1BKnOZcUsZZkbGMUJLmsKAlhSnlEJ8mb_a6XWO9GO3xArEcQkowIZFY7YnSyq3onNnFcYWVRtwXrKuFdMGoRos0escYxxBXaSYJ4xVmuKQV5SkqKlVGrY_ja32x06XSbXCymYhOb1qzEbW9ERlncaQ8CrwdBZz93Wsf_vHlkapl_JVpKxvF1M54Jc4zgjGFCA_U_C9UXKXeGRUDUplYnzS8nzREJujbUMvee7H6_u3_2fWvKfvugN1o2YSNt00_xMFPwWwPKme9d7p6dA5BMeT7wQ0x5FuM-Y5trw9df2x6CDT-AwYy8vo</recordid><startdate>20160519</startdate><enddate>20160519</enddate><creator>Wang, Juan</creator><creator>Chen, Xin</creator><creator>Wang, Fang</creator><creator>Zhang, Jieping</creator><creator>Li, Peng</creator><creator>Li, Zongyi</creator><creator>Xu, Jingying</creator><creator>Gao, Furong</creator><creator>Jin, Caixia</creator><creator>Tian, Haibin</creator><creator>Zhang, Jingfa</creator><creator>Li, Weiye</creator><creator>Lu, Lixia</creator><creator>Xu, Guo-Tong</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>IOV</scope><scope>ISR</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>5PM</scope><scope>DOA</scope></search><sort><creationdate>20160519</creationdate><title>OFD1, as a Ciliary Protein, Exhibits Neuroprotective Function in Photoreceptor Degeneration Models</title><author>Wang, Juan ; Chen, Xin ; Wang, Fang ; Zhang, Jieping ; Li, Peng ; Li, Zongyi ; Xu, Jingying ; Gao, Furong ; Jin, Caixia ; Tian, Haibin ; Zhang, Jingfa ; Li, Weiye ; Lu, Lixia ; Xu, Guo-Tong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c758t-83de3908123bb8587cf5bbd93201431770aa3298a6787b474565290b6d6026803</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Animal models</topic><topic>Animals</topic><topic>Antioxidants - metabolism</topic><topic>Apoptosis</topic><topic>Biology and Life Sciences</topic><topic>Cell Death</topic><topic>Cell Line</topic><topic>Cell Separation</topic><topic>Cilia</topic><topic>Cilia - metabolism</topic><topic>Ciliopathies</topic><topic>Congenital diseases</topic><topic>Degeneration</topic><topic>Development and progression</topic><topic>Disease</topic><topic>Electroretinography</topic><topic>Flow Cytometry</topic><topic>Fluorescence</topic><topic>Gene expression</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Hospitals</topic><topic>Immunocytochemistry</topic><topic>Immunofluorescence</topic><topic>Immunohistochemistry</topic><topic>Localization</topic><topic>Medical personnel</topic><topic>Medical research</topic><topic>Medicine</topic><topic>Medicine and Health Sciences</topic><topic>Methylnitrosourea - pharmacology</topic><topic>Mice</topic><topic>Multiple abnormalities</topic><topic>Mutation</topic><topic>N-Methyl-N-nitrosourea</topic><topic>Neuroprotection</topic><topic>Oxidative Stress</topic><topic>Oxygen</topic><topic>Photoreceptor Cells - pathology</topic><topic>Photoreceptor Cells, Vertebrate - metabolism</topic><topic>Photoreceptors</topic><topic>Physiological aspects</topic><topic>Plasmids - metabolism</topic><topic>Proteins</topic><topic>Proteins - genetics</topic><topic>Rats</topic><topic>Reactive oxygen species</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>Retina</topic><topic>Retina - metabolism</topic><topic>Retina - pathology</topic><topic>Retinal degeneration</topic><topic>Retinal Degeneration - metabolism</topic><topic>Retinal Degeneration - pathology</topic><topic>Retinitis</topic><topic>Retinitis pigmentosa</topic><topic>Retinitis Pigmentosa - genetics</topic><topic>Retinitis Pigmentosa - metabolism</topic><topic>Risk factors</topic><topic>RNA, Small Interfering - metabolism</topic><topic>Satellites</topic><topic>Signal Transduction</topic><topic>Signaling</topic><topic>Social Sciences</topic><topic>Stem cells</topic><topic>Stem Cells - cytology</topic><topic>Therapeutic applications</topic><topic>Toxicity</topic><topic>Western blotting</topic><topic>Wnt protein</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Juan</creatorcontrib><creatorcontrib>Chen, Xin</creatorcontrib><creatorcontrib>Wang, Fang</creatorcontrib><creatorcontrib>Zhang, Jieping</creatorcontrib><creatorcontrib>Li, Peng</creatorcontrib><creatorcontrib>Li, Zongyi</creatorcontrib><creatorcontrib>Xu, Jingying</creatorcontrib><creatorcontrib>Gao, Furong</creatorcontrib><creatorcontrib>Jin, Caixia</creatorcontrib><creatorcontrib>Tian, Haibin</creatorcontrib><creatorcontrib>Zhang, Jingfa</creatorcontrib><creatorcontrib>Li, Weiye</creatorcontrib><creatorcontrib>Lu, Lixia</creatorcontrib><creatorcontrib>Xu, Guo-Tong</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</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>Wang, Juan</au><au>Chen, Xin</au><au>Wang, Fang</au><au>Zhang, Jieping</au><au>Li, Peng</au><au>Li, Zongyi</au><au>Xu, Jingying</au><au>Gao, Furong</au><au>Jin, Caixia</au><au>Tian, Haibin</au><au>Zhang, Jingfa</au><au>Li, Weiye</au><au>Lu, Lixia</au><au>Xu, Guo-Tong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>OFD1, as a Ciliary Protein, Exhibits Neuroprotective Function in Photoreceptor Degeneration Models</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2016-05-19</date><risdate>2016</risdate><volume>11</volume><issue>5</issue><spage>e0155860</spage><pages>e0155860-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Ofd1 is a newly identified causative gene for Retinitis pigmentosa (RP), a photoreceptor degenerative disease. This study aimed to examine Ofd1 localization in retina and further to investigate its function in photoreceptor degeneration models. Ofd1 localization in rat retina was examined using immunofluorescence. N-methyl-N-nitrosourea (MNU)-induced rats and Royal College of Surgeons (RCS) rats were used as photoreceptor degeneration models. The expression pattern of Ofd1, other ciliary associated genes and Wnt signaling pathway genes were examined in rat models. Furthermore, pEGFP-Ofd1-CDS and pSUPER-Ofd1-shRNA were constructed to overexpress and knockdown the expression level in 661W and R28 cells. MNU was also used to induce cell death. Cilia formation was observed using immunocytochemistry (ICC). Reactive oxygen species (ROS) were detected using the 2', 7'-Dichlorofluorescin diacetate (DCFH-DA) assay. Apoptosis genes expression was examined using qRT-PCR, Western blotting and fluorescence-activated cell sorting (FACS). Ofd1 localized to outer segments of rat retina photoreceptors. Ofd1 and other ciliary proteins expression levels increased from the 1st and 4th postnatal weeks and decreased until the 6th week in the RCS rats, while their expression consistently decreased from the 1st and 7th day in the MNU rats. Moreover, Wnt signaling pathway proteins expression was significantly up-regulated in both rat models. Knockdown of Ofd1 expression resulted in a smaller population, shorter length of cell cilia, and lower cell viability. Ofd1 overexpression partially attenuated MNU toxic effects by reducing ROS levels and mitigating apoptosis. To the best of our knowledge, this is the first study demonstrating Ofd1 localization and its function in rat retina and in retinal degeneration rat models. Ofd1 plays a role in controlling photoreceptor cilium length and number. Importantly, it demonstrates a neuroprotective function by protecting the photoreceptor from oxidative stress and apoptosis. These data have expanded our understanding of Ofd1 function beyond cilia, and we concluded that ofd1 neuroprotection could be a potential treatment strategy in retina degeneration models.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>27196396</pmid><doi>10.1371/journal.pone.0155860</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2016-05, Vol.11 (5), p.e0155860 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1790065355 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Animal models Animals Antioxidants - metabolism Apoptosis Biology and Life Sciences Cell Death Cell Line Cell Separation Cilia Cilia - metabolism Ciliopathies Congenital diseases Degeneration Development and progression Disease Electroretinography Flow Cytometry Fluorescence Gene expression Genes Genetic aspects Hospitals Immunocytochemistry Immunofluorescence Immunohistochemistry Localization Medical personnel Medical research Medicine Medicine and Health Sciences Methylnitrosourea - pharmacology Mice Multiple abnormalities Mutation N-Methyl-N-nitrosourea Neuroprotection Oxidative Stress Oxygen Photoreceptor Cells - pathology Photoreceptor Cells, Vertebrate - metabolism Photoreceptors Physiological aspects Plasmids - metabolism Proteins Proteins - genetics Rats Reactive oxygen species Reactive Oxygen Species - metabolism Retina Retina - metabolism Retina - pathology Retinal degeneration Retinal Degeneration - metabolism Retinal Degeneration - pathology Retinitis Retinitis pigmentosa Retinitis Pigmentosa - genetics Retinitis Pigmentosa - metabolism Risk factors RNA, Small Interfering - metabolism Satellites Signal Transduction Signaling Social Sciences Stem cells Stem Cells - cytology Therapeutic applications Toxicity Western blotting Wnt protein |
| title | OFD1, as a Ciliary Protein, Exhibits Neuroprotective Function in Photoreceptor Degeneration Models |
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