Neuroprotective effect of transretinal electrical stimulation on neurons in the inner nuclear layer of the degenerated retina
Abstract Electrical stimulation has been shown to have neuroprotective effects on ganglion cells and photoreceptors in axotomized and dystrophic retinas from Royal College of Surgeons (RCS) rats. This study determined whether electrical stimulation also has a neuroprotective effect on cells in the i...
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description | Abstract Electrical stimulation has been shown to have neuroprotective effects on ganglion cells and photoreceptors in axotomized and dystrophic retinas from Royal College of Surgeons (RCS) rats. This study determined whether electrical stimulation also has a neuroprotective effect on cells in the inner nuclear layer (INL) of retinas. We cultivated retinas from adult RCS rats on microelectrode arrays and stimulated them continuously with 20 Hz for up to 5 days. Afterwards, we subjected them to quantitative immunohistochemical analysis. Using TUNEL assay we found that transretinal electrical stimulation (TRES) with charge densities within the range of 100–500 μC/cm2 reduced apoptosis of neurons in the INL of degenerated retinas from RCS −/− rats by 20% after 1 day of continuous stimulation. Antibody staining (OX-42, ED1) revealed a reduced activation of migroglial cells in RCS −/− and congenic control (RCS +/+) rat retinas by up to 50% after 1 day of stimulation. The effect of electrical stimulation on apoptosis and reduced activation of microglial cells was closely correlated with the strength and duration of the stimulation. The neuroprotective effect of TRES on neuronal cells in the INL of degenerated RCS rat retinas supports the idea that electrical stimulation may be a therapeutic option to delay the progression of retinal degeneration in patients suffering from retinitis pigmentosa. |
doi_str_mv | 10.1016/j.brainresbull.2008.12.013 |
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This study determined whether electrical stimulation also has a neuroprotective effect on cells in the inner nuclear layer (INL) of retinas. We cultivated retinas from adult RCS rats on microelectrode arrays and stimulated them continuously with 20 Hz for up to 5 days. Afterwards, we subjected them to quantitative immunohistochemical analysis. Using TUNEL assay we found that transretinal electrical stimulation (TRES) with charge densities within the range of 100–500 μC/cm2 reduced apoptosis of neurons in the INL of degenerated retinas from RCS −/− rats by 20% after 1 day of continuous stimulation. Antibody staining (OX-42, ED1) revealed a reduced activation of migroglial cells in RCS −/− and congenic control (RCS +/+) rat retinas by up to 50% after 1 day of stimulation. The effect of electrical stimulation on apoptosis and reduced activation of microglial cells was closely correlated with the strength and duration of the stimulation. The neuroprotective effect of TRES on neuronal cells in the INL of degenerated RCS rat retinas supports the idea that electrical stimulation may be a therapeutic option to delay the progression of retinal degeneration in patients suffering from retinitis pigmentosa.</description><identifier>ISSN: 0361-9230</identifier><identifier>EISSN: 1873-2747</identifier><identifier>DOI: 10.1016/j.brainresbull.2008.12.013</identifier><identifier>PMID: 19150490</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Apoptosis ; Apoptosis - physiology ; Cell Survival - physiology ; Cells, Cultured ; Electric Stimulation Therapy ; Electrical stimulation ; Immunohistochemistry ; In Situ Nick-End Labeling ; Microelectrode array ; Microelectrodes ; Microglia - physiology ; Neurology ; Neuroprotection ; Rats ; Rats, Mutant Strains ; Retina - physiopathology ; Retinal degeneration ; Retinal Degeneration - physiopathology ; Retinal Degeneration - therapy ; Retinal Neurons - physiology ; Retinal tissue culture</subject><ispartof>Brain research bulletin, 2009-04, Vol.79 (1), p.15-25</ispartof><rights>Elsevier Inc.</rights><rights>2009 Elsevier Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c433t-2c850a9b7cbc92c58e160dcf6de54202bca09a7e98191d3878b33157598fb4ff3</citedby><cites>FETCH-LOGICAL-c433t-2c850a9b7cbc92c58e160dcf6de54202bca09a7e98191d3878b33157598fb4ff3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0361923008004231$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19150490$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Schmid, Heiko</creatorcontrib><creatorcontrib>Herrmann, Thoralf</creatorcontrib><creatorcontrib>Kohler, Konrad</creatorcontrib><creatorcontrib>Stett, Alfred</creatorcontrib><title>Neuroprotective effect of transretinal electrical stimulation on neurons in the inner nuclear layer of the degenerated retina</title><title>Brain research bulletin</title><addtitle>Brain Res Bull</addtitle><description>Abstract Electrical stimulation has been shown to have neuroprotective effects on ganglion cells and photoreceptors in axotomized and dystrophic retinas from Royal College of Surgeons (RCS) rats. This study determined whether electrical stimulation also has a neuroprotective effect on cells in the inner nuclear layer (INL) of retinas. We cultivated retinas from adult RCS rats on microelectrode arrays and stimulated them continuously with 20 Hz for up to 5 days. Afterwards, we subjected them to quantitative immunohistochemical analysis. Using TUNEL assay we found that transretinal electrical stimulation (TRES) with charge densities within the range of 100–500 μC/cm2 reduced apoptosis of neurons in the INL of degenerated retinas from RCS −/− rats by 20% after 1 day of continuous stimulation. Antibody staining (OX-42, ED1) revealed a reduced activation of migroglial cells in RCS −/− and congenic control (RCS +/+) rat retinas by up to 50% after 1 day of stimulation. The effect of electrical stimulation on apoptosis and reduced activation of microglial cells was closely correlated with the strength and duration of the stimulation. The neuroprotective effect of TRES on neuronal cells in the INL of degenerated RCS rat retinas supports the idea that electrical stimulation may be a therapeutic option to delay the progression of retinal degeneration in patients suffering from retinitis pigmentosa.</description><subject>Animals</subject><subject>Apoptosis</subject><subject>Apoptosis - physiology</subject><subject>Cell Survival - physiology</subject><subject>Cells, Cultured</subject><subject>Electric Stimulation Therapy</subject><subject>Electrical stimulation</subject><subject>Immunohistochemistry</subject><subject>In Situ Nick-End Labeling</subject><subject>Microelectrode array</subject><subject>Microelectrodes</subject><subject>Microglia - physiology</subject><subject>Neurology</subject><subject>Neuroprotection</subject><subject>Rats</subject><subject>Rats, Mutant Strains</subject><subject>Retina - physiopathology</subject><subject>Retinal degeneration</subject><subject>Retinal Degeneration - physiopathology</subject><subject>Retinal Degeneration - therapy</subject><subject>Retinal Neurons - physiology</subject><subject>Retinal tissue culture</subject><issn>0361-9230</issn><issn>1873-2747</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNUk2LFDEQDaK44-pfkODBW7eVpD8SD4Ls-gWLHtRzSKcrmjGTXpP0whz876aZAcWTEKhK6tUr3ksR8oxBy4ANL_btlIyPCfO0htByANky3gIT98iOyVE0fOzG-2QHYmCN4gIuyKOc9wAwyH54SC6YYj10Cnbk10dc03KbloK2-Duk6FzN6OJoSSbmhMVHEyiG-pq8rWku_rAGU_wSaT1xI4iZ-kjLd6whYqJxtQFNosEc620jq6UZv2EtmoIzPfE-Jg-cCRmfnOMl-fr2zZer983Np3cfrl7fNLYTojTcyh6MmkY7WcVtL5ENMFs3zNh3HPhkDSgzopJV2CzkKCchWD_2Srqpc05ckucn3ir054q56IPPFkMwEZc162FQnVS9rMCXJ6BNS67inb5N_mDSUTPQm_l6r_82X2_ma8Z1Nb82Pz1PWacDzn9az25XwPUJgFXrnceks_UYLc4-VXv1vPj_m_PqHxobfNz-5gceMe-XNdUvy5rpXBv0520Nti0ACdBxwcRvf_G1AQ</recordid><startdate>20090406</startdate><enddate>20090406</enddate><creator>Schmid, Heiko</creator><creator>Herrmann, Thoralf</creator><creator>Kohler, Konrad</creator><creator>Stett, Alfred</creator><general>Elsevier Inc</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>7X8</scope></search><sort><creationdate>20090406</creationdate><title>Neuroprotective effect of transretinal electrical stimulation on neurons in the inner nuclear layer of the degenerated retina</title><author>Schmid, Heiko ; Herrmann, Thoralf ; Kohler, Konrad ; Stett, Alfred</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c433t-2c850a9b7cbc92c58e160dcf6de54202bca09a7e98191d3878b33157598fb4ff3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Animals</topic><topic>Apoptosis</topic><topic>Apoptosis - physiology</topic><topic>Cell Survival - physiology</topic><topic>Cells, Cultured</topic><topic>Electric Stimulation Therapy</topic><topic>Electrical stimulation</topic><topic>Immunohistochemistry</topic><topic>In Situ Nick-End Labeling</topic><topic>Microelectrode array</topic><topic>Microelectrodes</topic><topic>Microglia - physiology</topic><topic>Neurology</topic><topic>Neuroprotection</topic><topic>Rats</topic><topic>Rats, Mutant Strains</topic><topic>Retina - physiopathology</topic><topic>Retinal degeneration</topic><topic>Retinal Degeneration - physiopathology</topic><topic>Retinal Degeneration - therapy</topic><topic>Retinal Neurons - physiology</topic><topic>Retinal tissue culture</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Schmid, Heiko</creatorcontrib><creatorcontrib>Herrmann, Thoralf</creatorcontrib><creatorcontrib>Kohler, Konrad</creatorcontrib><creatorcontrib>Stett, Alfred</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Brain research bulletin</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Schmid, Heiko</au><au>Herrmann, Thoralf</au><au>Kohler, Konrad</au><au>Stett, Alfred</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Neuroprotective effect of transretinal electrical stimulation on neurons in the inner nuclear layer of the degenerated retina</atitle><jtitle>Brain research bulletin</jtitle><addtitle>Brain Res Bull</addtitle><date>2009-04-06</date><risdate>2009</risdate><volume>79</volume><issue>1</issue><spage>15</spage><epage>25</epage><pages>15-25</pages><issn>0361-9230</issn><eissn>1873-2747</eissn><abstract>Abstract Electrical stimulation has been shown to have neuroprotective effects on ganglion cells and photoreceptors in axotomized and dystrophic retinas from Royal College of Surgeons (RCS) rats. This study determined whether electrical stimulation also has a neuroprotective effect on cells in the inner nuclear layer (INL) of retinas. We cultivated retinas from adult RCS rats on microelectrode arrays and stimulated them continuously with 20 Hz for up to 5 days. Afterwards, we subjected them to quantitative immunohistochemical analysis. Using TUNEL assay we found that transretinal electrical stimulation (TRES) with charge densities within the range of 100–500 μC/cm2 reduced apoptosis of neurons in the INL of degenerated retinas from RCS −/− rats by 20% after 1 day of continuous stimulation. Antibody staining (OX-42, ED1) revealed a reduced activation of migroglial cells in RCS −/− and congenic control (RCS +/+) rat retinas by up to 50% after 1 day of stimulation. The effect of electrical stimulation on apoptosis and reduced activation of microglial cells was closely correlated with the strength and duration of the stimulation. The neuroprotective effect of TRES on neuronal cells in the INL of degenerated RCS rat retinas supports the idea that electrical stimulation may be a therapeutic option to delay the progression of retinal degeneration in patients suffering from retinitis pigmentosa.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>19150490</pmid><doi>10.1016/j.brainresbull.2008.12.013</doi><tpages>11</tpages></addata></record> |
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subjects | Animals Apoptosis Apoptosis - physiology Cell Survival - physiology Cells, Cultured Electric Stimulation Therapy Electrical stimulation Immunohistochemistry In Situ Nick-End Labeling Microelectrode array Microelectrodes Microglia - physiology Neurology Neuroprotection Rats Rats, Mutant Strains Retina - physiopathology Retinal degeneration Retinal Degeneration - physiopathology Retinal Degeneration - therapy Retinal Neurons - physiology Retinal tissue culture |
title | Neuroprotective effect of transretinal electrical stimulation on neurons in the inner nuclear layer of the degenerated retina |
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