The Peptides ADNF-9 and NAP Increase Survival and Neurite Outgrowth of Rat Retinal Ganglion Cells In Vitro
Recent studies demonstrated that short peptides derived from activity-dependent neurotrophic factor (ADNF) and activity-dependent neuroprotective protein (ADNP) are neuroprotective at femtomolar concentrations. We evaluated these findings in cultures of purified rat retinal ganglion cells (RGCs) usi...
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| Veröffentlicht in: | Investigative ophthalmology & visual science 2005-03, Vol.46 (3), p.933-938 |
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| creator | Lagreze, Wolf A Pielen, Amelie Steingart, Ruth Schlunck, Gunther Hofmann, Hans-Dieter Gozes, Illana Kirsch, Matthias |
| description | Recent studies demonstrated that short peptides derived from activity-dependent neurotrophic factor (ADNF) and activity-dependent neuroprotective protein (ADNP) are neuroprotective at femtomolar concentrations. We evaluated these findings in cultures of purified rat retinal ganglion cells (RGCs) using two such peptides: ADNF-9 and NAP. In a second step, the influence of these peptides on neurite outgrowth in retinal explants was investigated.
Retinal ganglion cells (RGCs) were purified from newborn (postnatal day [P]0-P2) rat retina by immunopanning with antibodies against Thy1.1 and were cultured in serum-free N2 medium for 2 days. RGCs were treated with ADNF-9 and NAP at concentrations ranging from 10(-18) to 10(-10) M. Survival was quantified by counting viable cells by phase-contrast microscopy. Retinal explants from postnatal (P9-P11) rats were cultured in three-dimensional fibrin clots in serum-free medium for 3 days. Explants were treated with 1 microM NAP or 1 microM ADNF-9. Neurite outgrowth was visualized by staining with Sudan black and quantified by measuring axonal length.
Both peptides enhanced survival of RGCs in a dose-dependent manner. ADNF-9 showed a maximum effect at 0.1 pM with an increase in survival to 177% (95% confidence interval: 149-204) of the control level. The EC(50) was 10.9 fM. NAP showed a maximum effect at 5 pM with an increase in survival to 167% (146-189) and an EC(50) of 6.1 fM. In the explants, 1 microM ADNF-9 enhanced axonal outgrowth to 126% (118-133) and 1 microM NAP to 117% (98-137) compared with the control.
Both peptides, ADNF-9 and NAP, not only increase RGC survival in vitro but also support neurite outgrowth in retinal explants. These peptides deserve further attention as potential neuroprotective compounds in retinal and optic nerve diseases. |
| doi_str_mv | 10.1167/iovs.04-0766 |
| format | Article |
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Retinal ganglion cells (RGCs) were purified from newborn (postnatal day [P]0-P2) rat retina by immunopanning with antibodies against Thy1.1 and were cultured in serum-free N2 medium for 2 days. RGCs were treated with ADNF-9 and NAP at concentrations ranging from 10(-18) to 10(-10) M. Survival was quantified by counting viable cells by phase-contrast microscopy. Retinal explants from postnatal (P9-P11) rats were cultured in three-dimensional fibrin clots in serum-free medium for 3 days. Explants were treated with 1 microM NAP or 1 microM ADNF-9. Neurite outgrowth was visualized by staining with Sudan black and quantified by measuring axonal length.
Both peptides enhanced survival of RGCs in a dose-dependent manner. ADNF-9 showed a maximum effect at 0.1 pM with an increase in survival to 177% (95% confidence interval: 149-204) of the control level. The EC(50) was 10.9 fM. NAP showed a maximum effect at 5 pM with an increase in survival to 167% (146-189) and an EC(50) of 6.1 fM. In the explants, 1 microM ADNF-9 enhanced axonal outgrowth to 126% (118-133) and 1 microM NAP to 117% (98-137) compared with the control.
Both peptides, ADNF-9 and NAP, not only increase RGC survival in vitro but also support neurite outgrowth in retinal explants. These peptides deserve further attention as potential neuroprotective compounds in retinal and optic nerve diseases.</description><identifier>ISSN: 0146-0404</identifier><identifier>ISSN: 1552-5783</identifier><identifier>EISSN: 1552-5783</identifier><identifier>DOI: 10.1167/iovs.04-0766</identifier><identifier>PMID: 15728550</identifier><identifier>CODEN: IOVSDA</identifier><language>eng</language><publisher>Rockville, MD: ARVO</publisher><subject>Animals ; Animals, Newborn ; Biological and medical sciences ; Brain-Derived Neurotrophic Factor - pharmacology ; Cell Proliferation ; Cell Survival - drug effects ; Cells, Cultured ; Ciliary Neurotrophic Factor - pharmacology ; Cytoprotection ; Dose-Response Relationship, Drug ; Eye and associated structures. Visual pathways and centers. Vision ; Fundamental and applied biological sciences. Psychology ; Microscopy, Phase-Contrast ; Nerve Tissue Proteins - pharmacology ; Neurites - physiology ; Neuroprotective Agents - pharmacology ; Oligopeptides - pharmacology ; Rats ; Rats, Sprague-Dawley ; Retinal Ganglion Cells - cytology ; Retinal Ganglion Cells - drug effects ; Vertebrates: nervous system and sense organs</subject><ispartof>Investigative ophthalmology & visual science, 2005-03, Vol.46 (3), p.933-938</ispartof><rights>2005 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c349t-f53fcc3d8a6cb79412d31fb36c3dcf01acf8a459073eb30a25a210a44873c1303</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16562445$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15728550$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lagreze, Wolf A</creatorcontrib><creatorcontrib>Pielen, Amelie</creatorcontrib><creatorcontrib>Steingart, Ruth</creatorcontrib><creatorcontrib>Schlunck, Gunther</creatorcontrib><creatorcontrib>Hofmann, Hans-Dieter</creatorcontrib><creatorcontrib>Gozes, Illana</creatorcontrib><creatorcontrib>Kirsch, Matthias</creatorcontrib><title>The Peptides ADNF-9 and NAP Increase Survival and Neurite Outgrowth of Rat Retinal Ganglion Cells In Vitro</title><title>Investigative ophthalmology & visual science</title><addtitle>Invest Ophthalmol Vis Sci</addtitle><description>Recent studies demonstrated that short peptides derived from activity-dependent neurotrophic factor (ADNF) and activity-dependent neuroprotective protein (ADNP) are neuroprotective at femtomolar concentrations. We evaluated these findings in cultures of purified rat retinal ganglion cells (RGCs) using two such peptides: ADNF-9 and NAP. In a second step, the influence of these peptides on neurite outgrowth in retinal explants was investigated.
Retinal ganglion cells (RGCs) were purified from newborn (postnatal day [P]0-P2) rat retina by immunopanning with antibodies against Thy1.1 and were cultured in serum-free N2 medium for 2 days. RGCs were treated with ADNF-9 and NAP at concentrations ranging from 10(-18) to 10(-10) M. Survival was quantified by counting viable cells by phase-contrast microscopy. Retinal explants from postnatal (P9-P11) rats were cultured in three-dimensional fibrin clots in serum-free medium for 3 days. Explants were treated with 1 microM NAP or 1 microM ADNF-9. Neurite outgrowth was visualized by staining with Sudan black and quantified by measuring axonal length.
Both peptides enhanced survival of RGCs in a dose-dependent manner. ADNF-9 showed a maximum effect at 0.1 pM with an increase in survival to 177% (95% confidence interval: 149-204) of the control level. The EC(50) was 10.9 fM. NAP showed a maximum effect at 5 pM with an increase in survival to 167% (146-189) and an EC(50) of 6.1 fM. In the explants, 1 microM ADNF-9 enhanced axonal outgrowth to 126% (118-133) and 1 microM NAP to 117% (98-137) compared with the control.
Both peptides, ADNF-9 and NAP, not only increase RGC survival in vitro but also support neurite outgrowth in retinal explants. These peptides deserve further attention as potential neuroprotective compounds in retinal and optic nerve diseases.</description><subject>Animals</subject><subject>Animals, Newborn</subject><subject>Biological and medical sciences</subject><subject>Brain-Derived Neurotrophic Factor - pharmacology</subject><subject>Cell Proliferation</subject><subject>Cell Survival - drug effects</subject><subject>Cells, Cultured</subject><subject>Ciliary Neurotrophic Factor - pharmacology</subject><subject>Cytoprotection</subject><subject>Dose-Response Relationship, Drug</subject><subject>Eye and associated structures. Visual pathways and centers. Vision</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Microscopy, Phase-Contrast</subject><subject>Nerve Tissue Proteins - pharmacology</subject><subject>Neurites - physiology</subject><subject>Neuroprotective Agents - pharmacology</subject><subject>Oligopeptides - pharmacology</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Retinal Ganglion Cells - cytology</subject><subject>Retinal Ganglion Cells - drug effects</subject><subject>Vertebrates: nervous system and sense organs</subject><issn>0146-0404</issn><issn>1552-5783</issn><issn>1552-5783</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpF0Mtr4zAQBnCxdNmmj9ueF126p7odWQ_bx5DddgulLX1dxUSWEhXHzkpyTP_7OiSQ08DMj4_hI-QngyvGVHHtu028ApFBodQ3MmFS5pksSn5EJsCEykCAOCYnMX4A5Izl8IMcM1nkpZQwIR-vS0uf7Dr52kY6_fNwk1UU25o-TJ_oXWuCxWjpSx82foPN7mL74JOlj31ahG5IS9o5-oyJPtvk2xHdYrtofNfSmW2aOKbQd59Cd0a-O2yiPd_PU_J28_d19i-7f7y9m03vM8NFlTInuTOG1yUqMy8qwfKaMzfnatwZBwyNK1HICgpu5xwwl5gzQCHKghvGgZ-S37vcdej-9zYmvfLRjK9ga7s-alUIqUrGR3i5gyZ0MQbr9Dr4FYZPzUBvu9XbbjUIve125L_2uf18ZesD3pc5gos9wGiwcQFb4-PBKalyIeTBLf1iOfhgdVxh04yxTA_DIJTmuuKcfwH0Yo33</recordid><startdate>20050301</startdate><enddate>20050301</enddate><creator>Lagreze, Wolf A</creator><creator>Pielen, Amelie</creator><creator>Steingart, Ruth</creator><creator>Schlunck, Gunther</creator><creator>Hofmann, Hans-Dieter</creator><creator>Gozes, Illana</creator><creator>Kirsch, Matthias</creator><general>ARVO</general><general>Association for Research in Vision and Ophtalmology</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>7X8</scope></search><sort><creationdate>20050301</creationdate><title>The Peptides ADNF-9 and NAP Increase Survival and Neurite Outgrowth of Rat Retinal Ganglion Cells In Vitro</title><author>Lagreze, Wolf A ; Pielen, Amelie ; Steingart, Ruth ; Schlunck, Gunther ; Hofmann, Hans-Dieter ; Gozes, Illana ; Kirsch, Matthias</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c349t-f53fcc3d8a6cb79412d31fb36c3dcf01acf8a459073eb30a25a210a44873c1303</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Animals</topic><topic>Animals, Newborn</topic><topic>Biological and medical sciences</topic><topic>Brain-Derived Neurotrophic Factor - pharmacology</topic><topic>Cell Proliferation</topic><topic>Cell Survival - drug effects</topic><topic>Cells, Cultured</topic><topic>Ciliary Neurotrophic Factor - pharmacology</topic><topic>Cytoprotection</topic><topic>Dose-Response Relationship, Drug</topic><topic>Eye and associated structures. Visual pathways and centers. Vision</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Microscopy, Phase-Contrast</topic><topic>Nerve Tissue Proteins - pharmacology</topic><topic>Neurites - physiology</topic><topic>Neuroprotective Agents - pharmacology</topic><topic>Oligopeptides - pharmacology</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Retinal Ganglion Cells - cytology</topic><topic>Retinal Ganglion Cells - drug effects</topic><topic>Vertebrates: nervous system and sense organs</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lagreze, Wolf A</creatorcontrib><creatorcontrib>Pielen, Amelie</creatorcontrib><creatorcontrib>Steingart, Ruth</creatorcontrib><creatorcontrib>Schlunck, Gunther</creatorcontrib><creatorcontrib>Hofmann, Hans-Dieter</creatorcontrib><creatorcontrib>Gozes, Illana</creatorcontrib><creatorcontrib>Kirsch, Matthias</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>MEDLINE - Academic</collection><jtitle>Investigative ophthalmology & visual science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lagreze, Wolf A</au><au>Pielen, Amelie</au><au>Steingart, Ruth</au><au>Schlunck, Gunther</au><au>Hofmann, Hans-Dieter</au><au>Gozes, Illana</au><au>Kirsch, Matthias</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Peptides ADNF-9 and NAP Increase Survival and Neurite Outgrowth of Rat Retinal Ganglion Cells In Vitro</atitle><jtitle>Investigative ophthalmology & visual science</jtitle><addtitle>Invest Ophthalmol Vis Sci</addtitle><date>2005-03-01</date><risdate>2005</risdate><volume>46</volume><issue>3</issue><spage>933</spage><epage>938</epage><pages>933-938</pages><issn>0146-0404</issn><issn>1552-5783</issn><eissn>1552-5783</eissn><coden>IOVSDA</coden><abstract>Recent studies demonstrated that short peptides derived from activity-dependent neurotrophic factor (ADNF) and activity-dependent neuroprotective protein (ADNP) are neuroprotective at femtomolar concentrations. We evaluated these findings in cultures of purified rat retinal ganglion cells (RGCs) using two such peptides: ADNF-9 and NAP. In a second step, the influence of these peptides on neurite outgrowth in retinal explants was investigated.
Retinal ganglion cells (RGCs) were purified from newborn (postnatal day [P]0-P2) rat retina by immunopanning with antibodies against Thy1.1 and were cultured in serum-free N2 medium for 2 days. RGCs were treated with ADNF-9 and NAP at concentrations ranging from 10(-18) to 10(-10) M. Survival was quantified by counting viable cells by phase-contrast microscopy. Retinal explants from postnatal (P9-P11) rats were cultured in three-dimensional fibrin clots in serum-free medium for 3 days. Explants were treated with 1 microM NAP or 1 microM ADNF-9. Neurite outgrowth was visualized by staining with Sudan black and quantified by measuring axonal length.
Both peptides enhanced survival of RGCs in a dose-dependent manner. ADNF-9 showed a maximum effect at 0.1 pM with an increase in survival to 177% (95% confidence interval: 149-204) of the control level. The EC(50) was 10.9 fM. NAP showed a maximum effect at 5 pM with an increase in survival to 167% (146-189) and an EC(50) of 6.1 fM. In the explants, 1 microM ADNF-9 enhanced axonal outgrowth to 126% (118-133) and 1 microM NAP to 117% (98-137) compared with the control.
Both peptides, ADNF-9 and NAP, not only increase RGC survival in vitro but also support neurite outgrowth in retinal explants. These peptides deserve further attention as potential neuroprotective compounds in retinal and optic nerve diseases.</abstract><cop>Rockville, MD</cop><pub>ARVO</pub><pmid>15728550</pmid><doi>10.1167/iovs.04-0766</doi><tpages>6</tpages></addata></record> |
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| subjects | Animals Animals, Newborn Biological and medical sciences Brain-Derived Neurotrophic Factor - pharmacology Cell Proliferation Cell Survival - drug effects Cells, Cultured Ciliary Neurotrophic Factor - pharmacology Cytoprotection Dose-Response Relationship, Drug Eye and associated structures. Visual pathways and centers. Vision Fundamental and applied biological sciences. Psychology Microscopy, Phase-Contrast Nerve Tissue Proteins - pharmacology Neurites - physiology Neuroprotective Agents - pharmacology Oligopeptides - pharmacology Rats Rats, Sprague-Dawley Retinal Ganglion Cells - cytology Retinal Ganglion Cells - drug effects Vertebrates: nervous system and sense organs |
| title | The Peptides ADNF-9 and NAP Increase Survival and Neurite Outgrowth of Rat Retinal Ganglion Cells In Vitro |
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