Neuroprotective effect of transcorneal electrical stimulation on light-induced photoreceptor degeneration
Direct electrical stimulation of neural tissues is a strategic approach to treat injured axons by accelerating their outgrowth [Al-Majed, A.A., Neumann, C.M., Brushart, T.M., Gordon, T., 2000. Brief electrical stimulation promotes the speed and accuracy of motor axonal regeneration. J. Neurosci. 20,...
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| description | Direct electrical stimulation of neural tissues is a strategic approach to treat injured axons by accelerating their outgrowth [Al-Majed, A.A., Neumann, C.M., Brushart, T.M., Gordon, T., 2000. Brief electrical stimulation promotes the speed and accuracy of motor axonal regeneration. J. Neurosci. 20, 2602–2608] and promoting their regeneration [Geremia, N.M., Gordon, T., Brushart, T.M., Al-Majed, A.A., Verge, V.M.K., 2007. Electrical stimulation promotes sensory neuron regeneration and growth-associated gene expression. Exp. Neurol. 205, 347–359]. Recently, transcorneal electrical stimulation (TCES), a novel less invasive method, has been shown to rescue axotomized and damaged retinal ganglion cells [Morimoto, T., Miyoshi, T., Matsuda, S., Tano, Y., Fujikado, T., Fukuda, Y., 2005. Transcorneal electrical stimulation rescues axotomized retinal ganglion cells by activating endogenous retinal IGF-1 system. Invest. Ophthalmol. Vis. Sci. 46(6), 2147–2155]. Here, we investigated the neuroprotection of TCES on light-induced photoreceptor degeneration and the underlying mechanism. Adult male Sprague–Dawley (SD) rats received TCES before (pre-TCES) or after (post-TCES) intense light exposure. After fourteen days of light exposure, retinal histology and electroretinography were performed to evaluate the neuroprotective effect of TCES. The mRNA and protein levels of apoptotic-associated genes including Bcl-2, Bax, Caspase-3 as well as ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF) in the retinas were determined by real-time PCR and Western blot analysis. The localization of these gene products in the retinas was examined by immunohistochemistry. Both pre- and post-TCES ameliorated the progressive photoreceptor degeneration. The degree of rescue depended on the strength of the electric charge. Post-TCES showed a relatively better and longer-term protective effect than pre-TCES. Real-time PCR and Western blot analysis revealed an upregulation of Bcl-2, CNTF, and BDNF and a downregulation of Bax in the retinas after TCES. Immunohistochemical studies showed that Bcl-2 and CNTF were selectively upregulated in Müller cells. These findings provide a new therapeutic method to prevent or delay photoreceptor degeneration through activating the intrinsic survival system. |
| doi_str_mv | 10.1016/j.expneurol.2009.06.016 |
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Brief electrical stimulation promotes the speed and accuracy of motor axonal regeneration. J. Neurosci. 20, 2602–2608] and promoting their regeneration [Geremia, N.M., Gordon, T., Brushart, T.M., Al-Majed, A.A., Verge, V.M.K., 2007. Electrical stimulation promotes sensory neuron regeneration and growth-associated gene expression. Exp. Neurol. 205, 347–359]. Recently, transcorneal electrical stimulation (TCES), a novel less invasive method, has been shown to rescue axotomized and damaged retinal ganglion cells [Morimoto, T., Miyoshi, T., Matsuda, S., Tano, Y., Fujikado, T., Fukuda, Y., 2005. Transcorneal electrical stimulation rescues axotomized retinal ganglion cells by activating endogenous retinal IGF-1 system. Invest. Ophthalmol. Vis. Sci. 46(6), 2147–2155]. Here, we investigated the neuroprotection of TCES on light-induced photoreceptor degeneration and the underlying mechanism. Adult male Sprague–Dawley (SD) rats received TCES before (pre-TCES) or after (post-TCES) intense light exposure. After fourteen days of light exposure, retinal histology and electroretinography were performed to evaluate the neuroprotective effect of TCES. The mRNA and protein levels of apoptotic-associated genes including Bcl-2, Bax, Caspase-3 as well as ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF) in the retinas were determined by real-time PCR and Western blot analysis. The localization of these gene products in the retinas was examined by immunohistochemistry. Both pre- and post-TCES ameliorated the progressive photoreceptor degeneration. The degree of rescue depended on the strength of the electric charge. Post-TCES showed a relatively better and longer-term protective effect than pre-TCES. Real-time PCR and Western blot analysis revealed an upregulation of Bcl-2, CNTF, and BDNF and a downregulation of Bax in the retinas after TCES. Immunohistochemical studies showed that Bcl-2 and CNTF were selectively upregulated in Müller cells. These findings provide a new therapeutic method to prevent or delay photoreceptor degeneration through activating the intrinsic survival system.</description><identifier>ISSN: 0014-4886</identifier><identifier>EISSN: 1090-2430</identifier><identifier>DOI: 10.1016/j.expneurol.2009.06.016</identifier><identifier>PMID: 19576889</identifier><identifier>CODEN: EXNEAC</identifier><language>eng</language><publisher>Amsterdam: Elsevier Inc</publisher><subject>Analysis of Variance ; Animals ; Apoptosis ; bcl-2-Associated X Protein - genetics ; bcl-2-Associated X Protein - metabolism ; Biological and medical sciences ; Biophysics ; Brain-Derived Neurotrophic Factor - genetics ; Brain-Derived Neurotrophic Factor - metabolism ; Caspase 3 - genetics ; Caspase 3 - metabolism ; Ciliary Neurotrophic Factor - genetics ; Ciliary Neurotrophic Factor - metabolism ; Cornea - physiology ; Disease Models, Animal ; Electric Stimulation Therapy - methods ; Electrical stimulation ; Electroretinography ; Gene Expression Regulation - physiology ; Light - adverse effects ; Light-induced ; Male ; Medical sciences ; Neurology ; Neuropharmacology ; Neuroprotective agent ; Neurotrophic factor ; Pharmacology. Drug treatments ; Photoreceptor Cells, Vertebrate - pathology ; Photoreceptor degeneration ; Proto-Oncogene Proteins c-bcl-2 - genetics ; Proto-Oncogene Proteins c-bcl-2 - metabolism ; Rats ; Rats, Sprague-Dawley ; Retina ; Retina - pathology ; Retina - physiopathology ; Retinal Degeneration - etiology ; Retinal Degeneration - pathology ; Retinal Degeneration - physiopathology ; Retinal Degeneration - therapy ; Time Factors</subject><ispartof>Experimental neurology, 2009-10, Vol.219 (2), p.439-452</ispartof><rights>2009 Elsevier Inc.</rights><rights>2009 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c496t-f3e5cd6769fc5f1acef6a254d9c92d2a8a7d92b7fad317cd930a1a83e45699d43</citedby><cites>FETCH-LOGICAL-c496t-f3e5cd6769fc5f1acef6a254d9c92d2a8a7d92b7fad317cd930a1a83e45699d43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.expneurol.2009.06.016$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21985830$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19576889$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ni, Ying-qin</creatorcontrib><creatorcontrib>Gan, De-kang</creatorcontrib><creatorcontrib>Xu, Hai-dong</creatorcontrib><creatorcontrib>Xu, Ge-zhi</creatorcontrib><creatorcontrib>Da, Cui-di</creatorcontrib><title>Neuroprotective effect of transcorneal electrical stimulation on light-induced photoreceptor degeneration</title><title>Experimental neurology</title><addtitle>Exp Neurol</addtitle><description>Direct electrical stimulation of neural tissues is a strategic approach to treat injured axons by accelerating their outgrowth [Al-Majed, A.A., Neumann, C.M., Brushart, T.M., Gordon, T., 2000. Brief electrical stimulation promotes the speed and accuracy of motor axonal regeneration. J. Neurosci. 20, 2602–2608] and promoting their regeneration [Geremia, N.M., Gordon, T., Brushart, T.M., Al-Majed, A.A., Verge, V.M.K., 2007. Electrical stimulation promotes sensory neuron regeneration and growth-associated gene expression. Exp. Neurol. 205, 347–359]. Recently, transcorneal electrical stimulation (TCES), a novel less invasive method, has been shown to rescue axotomized and damaged retinal ganglion cells [Morimoto, T., Miyoshi, T., Matsuda, S., Tano, Y., Fujikado, T., Fukuda, Y., 2005. Transcorneal electrical stimulation rescues axotomized retinal ganglion cells by activating endogenous retinal IGF-1 system. Invest. Ophthalmol. Vis. Sci. 46(6), 2147–2155]. Here, we investigated the neuroprotection of TCES on light-induced photoreceptor degeneration and the underlying mechanism. Adult male Sprague–Dawley (SD) rats received TCES before (pre-TCES) or after (post-TCES) intense light exposure. After fourteen days of light exposure, retinal histology and electroretinography were performed to evaluate the neuroprotective effect of TCES. The mRNA and protein levels of apoptotic-associated genes including Bcl-2, Bax, Caspase-3 as well as ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF) in the retinas were determined by real-time PCR and Western blot analysis. The localization of these gene products in the retinas was examined by immunohistochemistry. Both pre- and post-TCES ameliorated the progressive photoreceptor degeneration. The degree of rescue depended on the strength of the electric charge. Post-TCES showed a relatively better and longer-term protective effect than pre-TCES. Real-time PCR and Western blot analysis revealed an upregulation of Bcl-2, CNTF, and BDNF and a downregulation of Bax in the retinas after TCES. Immunohistochemical studies showed that Bcl-2 and CNTF were selectively upregulated in Müller cells. These findings provide a new therapeutic method to prevent or delay photoreceptor degeneration through activating the intrinsic survival system.</description><subject>Analysis of Variance</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>bcl-2-Associated X Protein - genetics</subject><subject>bcl-2-Associated X Protein - metabolism</subject><subject>Biological and medical sciences</subject><subject>Biophysics</subject><subject>Brain-Derived Neurotrophic Factor - genetics</subject><subject>Brain-Derived Neurotrophic Factor - metabolism</subject><subject>Caspase 3 - genetics</subject><subject>Caspase 3 - metabolism</subject><subject>Ciliary Neurotrophic Factor - genetics</subject><subject>Ciliary Neurotrophic Factor - metabolism</subject><subject>Cornea - physiology</subject><subject>Disease Models, Animal</subject><subject>Electric Stimulation Therapy - methods</subject><subject>Electrical stimulation</subject><subject>Electroretinography</subject><subject>Gene Expression Regulation - physiology</subject><subject>Light - adverse effects</subject><subject>Light-induced</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Neurology</subject><subject>Neuropharmacology</subject><subject>Neuroprotective agent</subject><subject>Neurotrophic factor</subject><subject>Pharmacology. Drug treatments</subject><subject>Photoreceptor Cells, Vertebrate - pathology</subject><subject>Photoreceptor degeneration</subject><subject>Proto-Oncogene Proteins c-bcl-2 - genetics</subject><subject>Proto-Oncogene Proteins c-bcl-2 - metabolism</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Retina</subject><subject>Retina - pathology</subject><subject>Retina - physiopathology</subject><subject>Retinal Degeneration - etiology</subject><subject>Retinal Degeneration - pathology</subject><subject>Retinal Degeneration - physiopathology</subject><subject>Retinal Degeneration - therapy</subject><subject>Time Factors</subject><issn>0014-4886</issn><issn>1090-2430</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1P3DAQhq0KVBboXyi50FuC7SSOfUSIfkiovZSz5bXH4FU2DraD6L_vbHe1PSJZmtHomXfG7xByxWjDKBM3mwbe5gmWFMeGU6oaKhqsfyArRhWtedfSE7KilHV1J6U4I-c5byiCHR8-kjOm-kFIqVYk_NyJzCkWsCW8QgXeY1ZFX5VkpmxjmsCMFYxYTcFimkvYLqMpIU4VvjE8PZc6TG6x4Kr5OZaYwMKMoXLwBBOkf-wlOfVmzPDpEC_I49f733ff64df337c3T7UtlOi1L6F3joxCOVt75mx4IXhfeeUVdxxI83gFF8P3riWDdaplhpmZAtdL5RyXXtBvux18VMvC-SityFbGEczQVyyRumeSs7eBTmjspdypzjsQZtizgm8nlPYmvRHM6p359AbfTyH3p1DU6Gxjp2fDyOW9Rbc_76D_whcHwCT0VuPltuQjxxnCldoKXK3ew7QudcASWcbYELHA5pdtIvh3WX-AuZwsT0</recordid><startdate>20091001</startdate><enddate>20091001</enddate><creator>Ni, Ying-qin</creator><creator>Gan, De-kang</creator><creator>Xu, Hai-dong</creator><creator>Xu, Ge-zhi</creator><creator>Da, Cui-di</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>IQODW</scope><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>7TK</scope><scope>7X8</scope></search><sort><creationdate>20091001</creationdate><title>Neuroprotective effect of transcorneal electrical stimulation on light-induced photoreceptor degeneration</title><author>Ni, Ying-qin ; Gan, De-kang ; Xu, Hai-dong ; Xu, Ge-zhi ; Da, Cui-di</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c496t-f3e5cd6769fc5f1acef6a254d9c92d2a8a7d92b7fad317cd930a1a83e45699d43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Analysis of Variance</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>bcl-2-Associated X Protein - genetics</topic><topic>bcl-2-Associated X Protein - metabolism</topic><topic>Biological and medical sciences</topic><topic>Biophysics</topic><topic>Brain-Derived Neurotrophic Factor - genetics</topic><topic>Brain-Derived Neurotrophic Factor - metabolism</topic><topic>Caspase 3 - genetics</topic><topic>Caspase 3 - metabolism</topic><topic>Ciliary Neurotrophic Factor - genetics</topic><topic>Ciliary Neurotrophic Factor - metabolism</topic><topic>Cornea - physiology</topic><topic>Disease Models, Animal</topic><topic>Electric Stimulation Therapy - methods</topic><topic>Electrical stimulation</topic><topic>Electroretinography</topic><topic>Gene Expression Regulation - physiology</topic><topic>Light - adverse effects</topic><topic>Light-induced</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Neurology</topic><topic>Neuropharmacology</topic><topic>Neuroprotective agent</topic><topic>Neurotrophic factor</topic><topic>Pharmacology. Drug treatments</topic><topic>Photoreceptor Cells, Vertebrate - pathology</topic><topic>Photoreceptor degeneration</topic><topic>Proto-Oncogene Proteins c-bcl-2 - genetics</topic><topic>Proto-Oncogene Proteins c-bcl-2 - metabolism</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Retina</topic><topic>Retina - pathology</topic><topic>Retina - physiopathology</topic><topic>Retinal Degeneration - etiology</topic><topic>Retinal Degeneration - pathology</topic><topic>Retinal Degeneration - physiopathology</topic><topic>Retinal Degeneration - therapy</topic><topic>Time Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ni, Ying-qin</creatorcontrib><creatorcontrib>Gan, De-kang</creatorcontrib><creatorcontrib>Xu, Hai-dong</creatorcontrib><creatorcontrib>Xu, Ge-zhi</creatorcontrib><creatorcontrib>Da, Cui-di</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Experimental neurology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ni, Ying-qin</au><au>Gan, De-kang</au><au>Xu, Hai-dong</au><au>Xu, Ge-zhi</au><au>Da, Cui-di</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Neuroprotective effect of transcorneal electrical stimulation on light-induced photoreceptor degeneration</atitle><jtitle>Experimental neurology</jtitle><addtitle>Exp Neurol</addtitle><date>2009-10-01</date><risdate>2009</risdate><volume>219</volume><issue>2</issue><spage>439</spage><epage>452</epage><pages>439-452</pages><issn>0014-4886</issn><eissn>1090-2430</eissn><coden>EXNEAC</coden><abstract>Direct electrical stimulation of neural tissues is a strategic approach to treat injured axons by accelerating their outgrowth [Al-Majed, A.A., Neumann, C.M., Brushart, T.M., Gordon, T., 2000. Brief electrical stimulation promotes the speed and accuracy of motor axonal regeneration. J. Neurosci. 20, 2602–2608] and promoting their regeneration [Geremia, N.M., Gordon, T., Brushart, T.M., Al-Majed, A.A., Verge, V.M.K., 2007. Electrical stimulation promotes sensory neuron regeneration and growth-associated gene expression. Exp. Neurol. 205, 347–359]. Recently, transcorneal electrical stimulation (TCES), a novel less invasive method, has been shown to rescue axotomized and damaged retinal ganglion cells [Morimoto, T., Miyoshi, T., Matsuda, S., Tano, Y., Fujikado, T., Fukuda, Y., 2005. Transcorneal electrical stimulation rescues axotomized retinal ganglion cells by activating endogenous retinal IGF-1 system. Invest. Ophthalmol. Vis. Sci. 46(6), 2147–2155]. Here, we investigated the neuroprotection of TCES on light-induced photoreceptor degeneration and the underlying mechanism. Adult male Sprague–Dawley (SD) rats received TCES before (pre-TCES) or after (post-TCES) intense light exposure. After fourteen days of light exposure, retinal histology and electroretinography were performed to evaluate the neuroprotective effect of TCES. The mRNA and protein levels of apoptotic-associated genes including Bcl-2, Bax, Caspase-3 as well as ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF) in the retinas were determined by real-time PCR and Western blot analysis. The localization of these gene products in the retinas was examined by immunohistochemistry. Both pre- and post-TCES ameliorated the progressive photoreceptor degeneration. The degree of rescue depended on the strength of the electric charge. Post-TCES showed a relatively better and longer-term protective effect than pre-TCES. Real-time PCR and Western blot analysis revealed an upregulation of Bcl-2, CNTF, and BDNF and a downregulation of Bax in the retinas after TCES. Immunohistochemical studies showed that Bcl-2 and CNTF were selectively upregulated in Müller cells. These findings provide a new therapeutic method to prevent or delay photoreceptor degeneration through activating the intrinsic survival system.</abstract><cop>Amsterdam</cop><pub>Elsevier Inc</pub><pmid>19576889</pmid><doi>10.1016/j.expneurol.2009.06.016</doi><tpages>14</tpages></addata></record> |
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| subjects | Analysis of Variance Animals Apoptosis bcl-2-Associated X Protein - genetics bcl-2-Associated X Protein - metabolism Biological and medical sciences Biophysics Brain-Derived Neurotrophic Factor - genetics Brain-Derived Neurotrophic Factor - metabolism Caspase 3 - genetics Caspase 3 - metabolism Ciliary Neurotrophic Factor - genetics Ciliary Neurotrophic Factor - metabolism Cornea - physiology Disease Models, Animal Electric Stimulation Therapy - methods Electrical stimulation Electroretinography Gene Expression Regulation - physiology Light - adverse effects Light-induced Male Medical sciences Neurology Neuropharmacology Neuroprotective agent Neurotrophic factor Pharmacology. Drug treatments Photoreceptor Cells, Vertebrate - pathology Photoreceptor degeneration Proto-Oncogene Proteins c-bcl-2 - genetics Proto-Oncogene Proteins c-bcl-2 - metabolism Rats Rats, Sprague-Dawley Retina Retina - pathology Retina - physiopathology Retinal Degeneration - etiology Retinal Degeneration - pathology Retinal Degeneration - physiopathology Retinal Degeneration - therapy Time Factors |
| title | Neuroprotective effect of transcorneal electrical stimulation on light-induced photoreceptor degeneration |
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