Neuroprotective Effect of Hepatocyte Growth Factor against Photoreceptor Degeneration in Rats
To determine whether hepatocyte growth factor (HGF) has a neuroprotective effect against photoreceptor degeneration in rats. Eight-week-old Sprague-Dawley (SD) and 24-day-old Royal College of Surgeons (RCS) rats received an intravitreal injection of HGF in the right eyes. The left eyes were injected...
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| Veröffentlicht in: | Investigative ophthalmology & visual science 2004-11, Vol.45 (11), p.4174-4182 |
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| container_title | Investigative ophthalmology & visual science |
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| creator | Machida, Shigeki Tanaka, Michiko Ishii, Takehisa Ohtaka, Kouji Takahashi, Tomomi Tazawa, Yutaka |
| description | To determine whether hepatocyte growth factor (HGF) has a neuroprotective effect against photoreceptor degeneration in rats.
Eight-week-old Sprague-Dawley (SD) and 24-day-old Royal College of Surgeons (RCS) rats received an intravitreal injection of HGF in the right eyes. The left eyes were injected with vehicle and served as the control. Two days after the injections, the SD rats were exposed to fluorescent light of 3000 lux for 72 hours. Scotopic and photopic electroretinograms (ERGs) were recorded 2 weeks after the light damage and at 70 days of age in RCS rats. After the ERG recordings, the animals were killed for histologic analysis. Some RCS rats were killed at 2 weeks after HGF-treatment for TdT-dUTP terminal nick-end labeling (TUNEL) studies.
In both light-damaged and RCS rats, the thresholds for the scotopic and photopic b-wave were significantly lower in the HGF-treated eyes than in the control eyes (P |
| doi_str_mv | 10.1167/iovs.04-0455 |
| format | Article |
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Eight-week-old Sprague-Dawley (SD) and 24-day-old Royal College of Surgeons (RCS) rats received an intravitreal injection of HGF in the right eyes. The left eyes were injected with vehicle and served as the control. Two days after the injections, the SD rats were exposed to fluorescent light of 3000 lux for 72 hours. Scotopic and photopic electroretinograms (ERGs) were recorded 2 weeks after the light damage and at 70 days of age in RCS rats. After the ERG recordings, the animals were killed for histologic analysis. Some RCS rats were killed at 2 weeks after HGF-treatment for TdT-dUTP terminal nick-end labeling (TUNEL) studies.
In both light-damaged and RCS rats, the thresholds for the scotopic and photopic b-wave were significantly lower in the HGF-treated eyes than in the control eyes (P <0.02). The maximum b-wave amplitudes (Vbmax) of the scotopic and photopic ERGs were significantly larger in the HGF-treated eyes (P <0.0005) with a significantly greater number of photoreceptor nuclei than in the control eyes in both animal models (P <0.005). The vehicle-injected eyes of RCS rats had significantly larger numbers of TUNEL-positive photoreceptor nuclei than the HGF-treated eyes (P=0.005).
Intravitreal HGF led to the morphologic and physiological preservation of photoreceptors in rats with photoreceptor degeneration induced by phototoxicity or a gene mutation. The antiapoptotic effect may be the mechanism for the neuroprotective action of HGF.</description><identifier>ISSN: 0146-0404</identifier><identifier>ISSN: 1552-5783</identifier><identifier>EISSN: 1552-5783</identifier><identifier>DOI: 10.1167/iovs.04-0455</identifier><identifier>PMID: 15505072</identifier><identifier>CODEN: IOVSDA</identifier><language>eng</language><publisher>Rockville, MD: ARVO</publisher><subject>Animals ; Biological and medical sciences ; Electroretinography ; Hepatocyte Growth Factor - pharmacology ; In Situ Nick-End Labeling ; Injections ; Light - adverse effects ; Male ; Medical sciences ; Neuroprotective Agents - pharmacology ; Ophthalmology ; Photoreceptor Cells, Vertebrate - drug effects ; Photoreceptor Cells, Vertebrate - physiology ; Photoreceptor Cells, Vertebrate - radiation effects ; Radiation Injuries, Experimental - etiology ; Radiation Injuries, Experimental - prevention & control ; Rats ; Rats, Mutant Strains ; Rats, Sprague-Dawley ; Retinal Degeneration - etiology ; Retinal Degeneration - genetics ; Retinal Degeneration - prevention & control ; Retinopathies ; Vitreous Body</subject><ispartof>Investigative ophthalmology & visual science, 2004-11, Vol.45 (11), p.4174-4182</ispartof><rights>2004 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c453t-9361c3d627b2e3d18aa94b6cfac9e86128103358485c59f170865736b20d7d603</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=16219420$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15505072$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Machida, Shigeki</creatorcontrib><creatorcontrib>Tanaka, Michiko</creatorcontrib><creatorcontrib>Ishii, Takehisa</creatorcontrib><creatorcontrib>Ohtaka, Kouji</creatorcontrib><creatorcontrib>Takahashi, Tomomi</creatorcontrib><creatorcontrib>Tazawa, Yutaka</creatorcontrib><title>Neuroprotective Effect of Hepatocyte Growth Factor against Photoreceptor Degeneration in Rats</title><title>Investigative ophthalmology & visual science</title><addtitle>Invest Ophthalmol Vis Sci</addtitle><description>To determine whether hepatocyte growth factor (HGF) has a neuroprotective effect against photoreceptor degeneration in rats.
Eight-week-old Sprague-Dawley (SD) and 24-day-old Royal College of Surgeons (RCS) rats received an intravitreal injection of HGF in the right eyes. The left eyes were injected with vehicle and served as the control. Two days after the injections, the SD rats were exposed to fluorescent light of 3000 lux for 72 hours. Scotopic and photopic electroretinograms (ERGs) were recorded 2 weeks after the light damage and at 70 days of age in RCS rats. After the ERG recordings, the animals were killed for histologic analysis. Some RCS rats were killed at 2 weeks after HGF-treatment for TdT-dUTP terminal nick-end labeling (TUNEL) studies.
In both light-damaged and RCS rats, the thresholds for the scotopic and photopic b-wave were significantly lower in the HGF-treated eyes than in the control eyes (P <0.02). The maximum b-wave amplitudes (Vbmax) of the scotopic and photopic ERGs were significantly larger in the HGF-treated eyes (P <0.0005) with a significantly greater number of photoreceptor nuclei than in the control eyes in both animal models (P <0.005). The vehicle-injected eyes of RCS rats had significantly larger numbers of TUNEL-positive photoreceptor nuclei than the HGF-treated eyes (P=0.005).
Intravitreal HGF led to the morphologic and physiological preservation of photoreceptors in rats with photoreceptor degeneration induced by phototoxicity or a gene mutation. The antiapoptotic effect may be the mechanism for the neuroprotective action of HGF.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Electroretinography</subject><subject>Hepatocyte Growth Factor - pharmacology</subject><subject>In Situ Nick-End Labeling</subject><subject>Injections</subject><subject>Light - adverse effects</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Neuroprotective Agents - pharmacology</subject><subject>Ophthalmology</subject><subject>Photoreceptor Cells, Vertebrate - drug effects</subject><subject>Photoreceptor Cells, Vertebrate - physiology</subject><subject>Photoreceptor Cells, Vertebrate - radiation effects</subject><subject>Radiation Injuries, Experimental - etiology</subject><subject>Radiation Injuries, Experimental - prevention & control</subject><subject>Rats</subject><subject>Rats, Mutant Strains</subject><subject>Rats, Sprague-Dawley</subject><subject>Retinal Degeneration - etiology</subject><subject>Retinal Degeneration - genetics</subject><subject>Retinal Degeneration - prevention & control</subject><subject>Retinopathies</subject><subject>Vitreous Body</subject><issn>0146-0404</issn><issn>1552-5783</issn><issn>1552-5783</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkF1LwzAUhoMoOqd3XktuxBs78932UuY-hKEieikhTdMtsjUlyVb2723ZYFfnnJeH98ADwB1GI4xF-mzdLowQSxDj_AwMMOck4WlGz8EAYSa6HLErcB3CH0IEY4IuwVUHIY5SMgC_72brXeNdNDranYGTquo26Co4N42KTu-jgTPv2riCU6Wj81Atla1DhJ8r151Gm6ZPX83S1MaraF0NbQ2_VAw34KJS62Buj3MIfqaT7_E8WXzM3sYvi0QzTmOSU4E1LQVJC2JoiTOlclYIXSmdm0xgkmFEKc9YxjXPK5yiTPCUioKgMi0FokPwdOjV3oXgTSUbbzfK7yVGsrcke0sSMdlb6vD7A95si40pT_BRSwc8HAEVtFpXXtXahhMnCM4Z6f8-HriVXa5a640MG7Ved7VYtm3LePdcMpwy-g84h33Y</recordid><startdate>20041101</startdate><enddate>20041101</enddate><creator>Machida, Shigeki</creator><creator>Tanaka, Michiko</creator><creator>Ishii, Takehisa</creator><creator>Ohtaka, Kouji</creator><creator>Takahashi, Tomomi</creator><creator>Tazawa, Yutaka</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></search><sort><creationdate>20041101</creationdate><title>Neuroprotective Effect of Hepatocyte Growth Factor against Photoreceptor Degeneration in Rats</title><author>Machida, Shigeki ; Tanaka, Michiko ; Ishii, Takehisa ; Ohtaka, Kouji ; Takahashi, Tomomi ; Tazawa, Yutaka</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c453t-9361c3d627b2e3d18aa94b6cfac9e86128103358485c59f170865736b20d7d603</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Electroretinography</topic><topic>Hepatocyte Growth Factor - pharmacology</topic><topic>In Situ Nick-End Labeling</topic><topic>Injections</topic><topic>Light - adverse effects</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Neuroprotective Agents - pharmacology</topic><topic>Ophthalmology</topic><topic>Photoreceptor Cells, Vertebrate - drug effects</topic><topic>Photoreceptor Cells, Vertebrate - physiology</topic><topic>Photoreceptor Cells, Vertebrate - radiation effects</topic><topic>Radiation Injuries, Experimental - etiology</topic><topic>Radiation Injuries, Experimental - prevention & control</topic><topic>Rats</topic><topic>Rats, Mutant Strains</topic><topic>Rats, Sprague-Dawley</topic><topic>Retinal Degeneration - etiology</topic><topic>Retinal Degeneration - genetics</topic><topic>Retinal Degeneration - prevention & control</topic><topic>Retinopathies</topic><topic>Vitreous Body</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Machida, Shigeki</creatorcontrib><creatorcontrib>Tanaka, Michiko</creatorcontrib><creatorcontrib>Ishii, Takehisa</creatorcontrib><creatorcontrib>Ohtaka, Kouji</creatorcontrib><creatorcontrib>Takahashi, Tomomi</creatorcontrib><creatorcontrib>Tazawa, Yutaka</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><jtitle>Investigative ophthalmology & visual science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Machida, Shigeki</au><au>Tanaka, Michiko</au><au>Ishii, Takehisa</au><au>Ohtaka, Kouji</au><au>Takahashi, Tomomi</au><au>Tazawa, Yutaka</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Neuroprotective Effect of Hepatocyte Growth Factor against Photoreceptor Degeneration in Rats</atitle><jtitle>Investigative ophthalmology & visual science</jtitle><addtitle>Invest Ophthalmol Vis Sci</addtitle><date>2004-11-01</date><risdate>2004</risdate><volume>45</volume><issue>11</issue><spage>4174</spage><epage>4182</epage><pages>4174-4182</pages><issn>0146-0404</issn><issn>1552-5783</issn><eissn>1552-5783</eissn><coden>IOVSDA</coden><abstract>To determine whether hepatocyte growth factor (HGF) has a neuroprotective effect against photoreceptor degeneration in rats.
Eight-week-old Sprague-Dawley (SD) and 24-day-old Royal College of Surgeons (RCS) rats received an intravitreal injection of HGF in the right eyes. The left eyes were injected with vehicle and served as the control. Two days after the injections, the SD rats were exposed to fluorescent light of 3000 lux for 72 hours. Scotopic and photopic electroretinograms (ERGs) were recorded 2 weeks after the light damage and at 70 days of age in RCS rats. After the ERG recordings, the animals were killed for histologic analysis. Some RCS rats were killed at 2 weeks after HGF-treatment for TdT-dUTP terminal nick-end labeling (TUNEL) studies.
In both light-damaged and RCS rats, the thresholds for the scotopic and photopic b-wave were significantly lower in the HGF-treated eyes than in the control eyes (P <0.02). The maximum b-wave amplitudes (Vbmax) of the scotopic and photopic ERGs were significantly larger in the HGF-treated eyes (P <0.0005) with a significantly greater number of photoreceptor nuclei than in the control eyes in both animal models (P <0.005). The vehicle-injected eyes of RCS rats had significantly larger numbers of TUNEL-positive photoreceptor nuclei than the HGF-treated eyes (P=0.005).
Intravitreal HGF led to the morphologic and physiological preservation of photoreceptors in rats with photoreceptor degeneration induced by phototoxicity or a gene mutation. The antiapoptotic effect may be the mechanism for the neuroprotective action of HGF.</abstract><cop>Rockville, MD</cop><pub>ARVO</pub><pmid>15505072</pmid><doi>10.1167/iovs.04-0455</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Biological and medical sciences Electroretinography Hepatocyte Growth Factor - pharmacology In Situ Nick-End Labeling Injections Light - adverse effects Male Medical sciences Neuroprotective Agents - pharmacology Ophthalmology Photoreceptor Cells, Vertebrate - drug effects Photoreceptor Cells, Vertebrate - physiology Photoreceptor Cells, Vertebrate - radiation effects Radiation Injuries, Experimental - etiology Radiation Injuries, Experimental - prevention & control Rats Rats, Mutant Strains Rats, Sprague-Dawley Retinal Degeneration - etiology Retinal Degeneration - genetics Retinal Degeneration - prevention & control Retinopathies Vitreous Body |
| title | Neuroprotective Effect of Hepatocyte Growth Factor against Photoreceptor Degeneration in Rats |
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