Systemic administration of the di-apocarotenoid norbixin (BIO201) is neuroprotective, preserves photoreceptor function and inhibits A2E and lipofuscin accumulation in animal models of age-related macular degeneration and Stargardt disease
Atrophic A\age-related macular degeneration (AMD) and Stargardt disease (STGD) are major blinding diseases affecting millions of patients worldwide, but no treatment is available. In dry AMD and STGD oxidative stress and subretinal accumulation of -retinylidene- -retinylethanolamine (A2E), a toxic b...
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| Veröffentlicht in: | Aging (Albany, NY.) NY.), 2020-04, Vol.12 (7), p.6151-6171 |
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| creator | Fontaine, Valérie Monteiro, Elodie Fournié, Mylène Brazhnikova, Elena Boumedine, Thinhinane Vidal, Cécile Balducci, Christine Guibout, Louis Latil, Mathilde Dilda, Pierre J Veillet, Stanislas Sahel, José-Alain Lafont, René Camelo, Serge |
| description | Atrophic A\age-related macular degeneration (AMD) and Stargardt disease (STGD) are major blinding diseases affecting millions of patients worldwide, but no treatment is available. In dry AMD and STGD oxidative stress and subretinal accumulation of
-retinylidene-
-retinylethanolamine (A2E), a toxic by-product of the visual cycle, causes retinal pigment epithelium (RPE) and photoreceptor degeneration leading to visual impairment. Acute and chronic retinal degeneration following blue light damage (BLD) in BALB/c mice and aging of
mice, respectively, reproduce features of AMD and STGD. Efficacy of systemic administrations of 9'-
-norbixin (norbixin), a natural di-apocarotenoid, prepared from
seeds with anti-oxidative properties, was evaluated during BLD in BALB/c mice, and in
mice of different ages, following three experimental designs: "preventive", "early curative" and "late curative" supplementations. Norbixin injected intraperitoneally in BALB/c mice, maintained scotopic and photopic electroretinogram amplitude and was neuroprotective. Norbixin chronic oral administration for 6 months in
mice following the "early curative" supplementation showed optimal neuroprotection and maintenance of photoreceptor function and reduced ocular A2E accumulation. Thus, norbixin appears promising as a systemic drug candidate for both AMD and STGD treatment. |
| doi_str_mv | 10.18632/aging.103014 |
| format | Article |
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-retinylidene-
-retinylethanolamine (A2E), a toxic by-product of the visual cycle, causes retinal pigment epithelium (RPE) and photoreceptor degeneration leading to visual impairment. Acute and chronic retinal degeneration following blue light damage (BLD) in BALB/c mice and aging of
mice, respectively, reproduce features of AMD and STGD. Efficacy of systemic administrations of 9'-
-norbixin (norbixin), a natural di-apocarotenoid, prepared from
seeds with anti-oxidative properties, was evaluated during BLD in BALB/c mice, and in
mice of different ages, following three experimental designs: "preventive", "early curative" and "late curative" supplementations. Norbixin injected intraperitoneally in BALB/c mice, maintained scotopic and photopic electroretinogram amplitude and was neuroprotective. Norbixin chronic oral administration for 6 months in
mice following the "early curative" supplementation showed optimal neuroprotection and maintenance of photoreceptor function and reduced ocular A2E accumulation. Thus, norbixin appears promising as a systemic drug candidate for both AMD and STGD treatment.</description><identifier>ISSN: 1945-4589</identifier><identifier>EISSN: 1945-4589</identifier><identifier>DOI: 10.18632/aging.103014</identifier><identifier>PMID: 32255762</identifier><language>eng</language><publisher>United States: Impact Journals</publisher><subject>Animals ; Carotenoids - pharmacology ; Drug Monitoring - methods ; Electroretinography - methods ; Human health and pathology ; Injections, Intraperitoneal ; Life Sciences ; Macular Degeneration - drug therapy ; Macular Degeneration - metabolism ; Macular Degeneration - prevention & control ; Mice ; Neuroprotective Agents - pharmacology ; Photoreceptor Cells, Vertebrate - drug effects ; Photoreceptor Cells, Vertebrate - metabolism ; Research Paper ; Retinoids - antagonists & inhibitors ; Retinoids - metabolism ; Stargardt Disease - drug therapy ; Stargardt Disease - metabolism ; Stargardt Disease - prevention & control ; Treatment Outcome</subject><ispartof>Aging (Albany, NY.), 2020-04, Vol.12 (7), p.6151-6171</ispartof><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><rights>Copyright © 2020 Fontaine et al.</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3364-e6951e1e589899bf9a90c85ebe59334dd5a17c8bce626eeb3cd8bce323c824463</citedby><cites>FETCH-LOGICAL-c3364-e6951e1e589899bf9a90c85ebe59334dd5a17c8bce626eeb3cd8bce323c824463</cites><orcidid>0000-0001-8005-1606 ; 0000-0002-8044-540X ; 0000-0001-9916-8513 ; 0000-0001-9541-2902 ; 0000-0002-4831-1153 ; 0000-0001-8733-8503</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7185133/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7185133/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32255762$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.sorbonne-universite.fr/hal-02617486$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Fontaine, Valérie</creatorcontrib><creatorcontrib>Monteiro, Elodie</creatorcontrib><creatorcontrib>Fournié, Mylène</creatorcontrib><creatorcontrib>Brazhnikova, Elena</creatorcontrib><creatorcontrib>Boumedine, Thinhinane</creatorcontrib><creatorcontrib>Vidal, Cécile</creatorcontrib><creatorcontrib>Balducci, Christine</creatorcontrib><creatorcontrib>Guibout, Louis</creatorcontrib><creatorcontrib>Latil, Mathilde</creatorcontrib><creatorcontrib>Dilda, Pierre J</creatorcontrib><creatorcontrib>Veillet, Stanislas</creatorcontrib><creatorcontrib>Sahel, José-Alain</creatorcontrib><creatorcontrib>Lafont, René</creatorcontrib><creatorcontrib>Camelo, Serge</creatorcontrib><title>Systemic administration of the di-apocarotenoid norbixin (BIO201) is neuroprotective, preserves photoreceptor function and inhibits A2E and lipofuscin accumulation in animal models of age-related macular degeneration and Stargardt disease</title><title>Aging (Albany, NY.)</title><addtitle>Aging (Albany NY)</addtitle><description>Atrophic A\age-related macular degeneration (AMD) and Stargardt disease (STGD) are major blinding diseases affecting millions of patients worldwide, but no treatment is available. In dry AMD and STGD oxidative stress and subretinal accumulation of
-retinylidene-
-retinylethanolamine (A2E), a toxic by-product of the visual cycle, causes retinal pigment epithelium (RPE) and photoreceptor degeneration leading to visual impairment. Acute and chronic retinal degeneration following blue light damage (BLD) in BALB/c mice and aging of
mice, respectively, reproduce features of AMD and STGD. Efficacy of systemic administrations of 9'-
-norbixin (norbixin), a natural di-apocarotenoid, prepared from
seeds with anti-oxidative properties, was evaluated during BLD in BALB/c mice, and in
mice of different ages, following three experimental designs: "preventive", "early curative" and "late curative" supplementations. Norbixin injected intraperitoneally in BALB/c mice, maintained scotopic and photopic electroretinogram amplitude and was neuroprotective. Norbixin chronic oral administration for 6 months in
mice following the "early curative" supplementation showed optimal neuroprotection and maintenance of photoreceptor function and reduced ocular A2E accumulation. Thus, norbixin appears promising as a systemic drug candidate for both AMD and STGD treatment.</description><subject>Animals</subject><subject>Carotenoids - pharmacology</subject><subject>Drug Monitoring - methods</subject><subject>Electroretinography - methods</subject><subject>Human health and pathology</subject><subject>Injections, Intraperitoneal</subject><subject>Life Sciences</subject><subject>Macular Degeneration - drug therapy</subject><subject>Macular Degeneration - metabolism</subject><subject>Macular Degeneration - prevention & control</subject><subject>Mice</subject><subject>Neuroprotective Agents - pharmacology</subject><subject>Photoreceptor Cells, Vertebrate - drug effects</subject><subject>Photoreceptor Cells, Vertebrate - metabolism</subject><subject>Research Paper</subject><subject>Retinoids - antagonists & inhibitors</subject><subject>Retinoids - metabolism</subject><subject>Stargardt Disease - drug therapy</subject><subject>Stargardt Disease - metabolism</subject><subject>Stargardt Disease - prevention & control</subject><subject>Treatment Outcome</subject><issn>1945-4589</issn><issn>1945-4589</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdksFO3DAQhqOqVaHQY6-Vj0VqaGzH3uRSaYtoQVqJA_RsOfYkcZXYke2s4KX7DHU2FAGn8Yy_-TUz-rPsEy7OccUp-SY7Y7tzXNACl2-yY1yXLC9ZVb999j7KPoTwpyg4YyV_nx1RQhjbcHKc_b19CBFGo5DUo7EmRC-jcRa5FsUekDa5nJyS3kWwzmhknW_MvbHoy4_rG1LgM2QCsjB7Ny2MimYPX9HkIYDfQ0BT76LzoGBKAbWzVQd5aTUytjeNiQFtyeWhMJjJtXNQSV0qNY_zsM6y5NaMckCj0zCEZTjZQe4hAaDRKFVCPdLQgYXHBRbB2yh9J72OaY8AMsBp9q6VQ4CPj_Ek-_3z8u7iKt_d_Lq-2O5yRSkvc-A1w4Ahna6q66atZV2oikEDrKa01JpJvFFVo4ATDtBQpZeEEqoqUpacnmTfV91pbkbQCmy66yAmn7bwD8JJI17-WNOLzu3FBlcMU5oEzlaB_lXb1XYnllpBON6UFd_jxOYrq7wLwUP71IALcTCJOJhErCZJ_Ofnwz3R_11B_wGQs8Cr</recordid><startdate>20200407</startdate><enddate>20200407</enddate><creator>Fontaine, Valérie</creator><creator>Monteiro, Elodie</creator><creator>Fournié, Mylène</creator><creator>Brazhnikova, Elena</creator><creator>Boumedine, Thinhinane</creator><creator>Vidal, Cécile</creator><creator>Balducci, Christine</creator><creator>Guibout, Louis</creator><creator>Latil, Mathilde</creator><creator>Dilda, Pierre J</creator><creator>Veillet, Stanislas</creator><creator>Sahel, José-Alain</creator><creator>Lafont, René</creator><creator>Camelo, Serge</creator><general>Impact Journals</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>1XC</scope><scope>VOOES</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-8005-1606</orcidid><orcidid>https://orcid.org/0000-0002-8044-540X</orcidid><orcidid>https://orcid.org/0000-0001-9916-8513</orcidid><orcidid>https://orcid.org/0000-0001-9541-2902</orcidid><orcidid>https://orcid.org/0000-0002-4831-1153</orcidid><orcidid>https://orcid.org/0000-0001-8733-8503</orcidid></search><sort><creationdate>20200407</creationdate><title>Systemic administration of the di-apocarotenoid norbixin (BIO201) is neuroprotective, preserves photoreceptor function and inhibits A2E and lipofuscin accumulation in animal models of age-related macular degeneration and Stargardt disease</title><author>Fontaine, Valérie ; Monteiro, Elodie ; Fournié, Mylène ; Brazhnikova, Elena ; Boumedine, Thinhinane ; Vidal, Cécile ; Balducci, Christine ; Guibout, Louis ; Latil, Mathilde ; Dilda, Pierre J ; Veillet, Stanislas ; Sahel, José-Alain ; Lafont, René ; Camelo, Serge</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3364-e6951e1e589899bf9a90c85ebe59334dd5a17c8bce626eeb3cd8bce323c824463</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Animals</topic><topic>Carotenoids - pharmacology</topic><topic>Drug Monitoring - methods</topic><topic>Electroretinography - methods</topic><topic>Human health and pathology</topic><topic>Injections, Intraperitoneal</topic><topic>Life Sciences</topic><topic>Macular Degeneration - drug therapy</topic><topic>Macular Degeneration - metabolism</topic><topic>Macular Degeneration - prevention & control</topic><topic>Mice</topic><topic>Neuroprotective Agents - pharmacology</topic><topic>Photoreceptor Cells, Vertebrate - drug effects</topic><topic>Photoreceptor Cells, Vertebrate - metabolism</topic><topic>Research Paper</topic><topic>Retinoids - antagonists & inhibitors</topic><topic>Retinoids - metabolism</topic><topic>Stargardt Disease - drug therapy</topic><topic>Stargardt Disease - metabolism</topic><topic>Stargardt Disease - prevention & control</topic><topic>Treatment Outcome</topic><toplevel>online_resources</toplevel><creatorcontrib>Fontaine, Valérie</creatorcontrib><creatorcontrib>Monteiro, Elodie</creatorcontrib><creatorcontrib>Fournié, Mylène</creatorcontrib><creatorcontrib>Brazhnikova, Elena</creatorcontrib><creatorcontrib>Boumedine, Thinhinane</creatorcontrib><creatorcontrib>Vidal, Cécile</creatorcontrib><creatorcontrib>Balducci, Christine</creatorcontrib><creatorcontrib>Guibout, Louis</creatorcontrib><creatorcontrib>Latil, Mathilde</creatorcontrib><creatorcontrib>Dilda, Pierre J</creatorcontrib><creatorcontrib>Veillet, Stanislas</creatorcontrib><creatorcontrib>Sahel, José-Alain</creatorcontrib><creatorcontrib>Lafont, René</creatorcontrib><creatorcontrib>Camelo, Serge</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>Hyper Article en Ligne (HAL) (Open Access)</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Aging (Albany, NY.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fontaine, Valérie</au><au>Monteiro, Elodie</au><au>Fournié, Mylène</au><au>Brazhnikova, Elena</au><au>Boumedine, Thinhinane</au><au>Vidal, Cécile</au><au>Balducci, Christine</au><au>Guibout, Louis</au><au>Latil, Mathilde</au><au>Dilda, Pierre J</au><au>Veillet, Stanislas</au><au>Sahel, José-Alain</au><au>Lafont, René</au><au>Camelo, Serge</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Systemic administration of the di-apocarotenoid norbixin (BIO201) is neuroprotective, preserves photoreceptor function and inhibits A2E and lipofuscin accumulation in animal models of age-related macular degeneration and Stargardt disease</atitle><jtitle>Aging (Albany, NY.)</jtitle><addtitle>Aging (Albany NY)</addtitle><date>2020-04-07</date><risdate>2020</risdate><volume>12</volume><issue>7</issue><spage>6151</spage><epage>6171</epage><pages>6151-6171</pages><issn>1945-4589</issn><eissn>1945-4589</eissn><abstract>Atrophic A\age-related macular degeneration (AMD) and Stargardt disease (STGD) are major blinding diseases affecting millions of patients worldwide, but no treatment is available. In dry AMD and STGD oxidative stress and subretinal accumulation of
-retinylidene-
-retinylethanolamine (A2E), a toxic by-product of the visual cycle, causes retinal pigment epithelium (RPE) and photoreceptor degeneration leading to visual impairment. Acute and chronic retinal degeneration following blue light damage (BLD) in BALB/c mice and aging of
mice, respectively, reproduce features of AMD and STGD. Efficacy of systemic administrations of 9'-
-norbixin (norbixin), a natural di-apocarotenoid, prepared from
seeds with anti-oxidative properties, was evaluated during BLD in BALB/c mice, and in
mice of different ages, following three experimental designs: "preventive", "early curative" and "late curative" supplementations. Norbixin injected intraperitoneally in BALB/c mice, maintained scotopic and photopic electroretinogram amplitude and was neuroprotective. Norbixin chronic oral administration for 6 months in
mice following the "early curative" supplementation showed optimal neuroprotection and maintenance of photoreceptor function and reduced ocular A2E accumulation. Thus, norbixin appears promising as a systemic drug candidate for both AMD and STGD treatment.</abstract><cop>United States</cop><pub>Impact Journals</pub><pmid>32255762</pmid><doi>10.18632/aging.103014</doi><tpages>21</tpages><orcidid>https://orcid.org/0000-0001-8005-1606</orcidid><orcidid>https://orcid.org/0000-0002-8044-540X</orcidid><orcidid>https://orcid.org/0000-0001-9916-8513</orcidid><orcidid>https://orcid.org/0000-0001-9541-2902</orcidid><orcidid>https://orcid.org/0000-0002-4831-1153</orcidid><orcidid>https://orcid.org/0000-0001-8733-8503</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Aging (Albany, NY.), 2020-04, Vol.12 (7), p.6151-6171 |
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| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7185133 |
| source | PubMed Central Free; MEDLINE; PubMed Central Open Access; EZB Electronic Journals Library |
| subjects | Animals Carotenoids - pharmacology Drug Monitoring - methods Electroretinography - methods Human health and pathology Injections, Intraperitoneal Life Sciences Macular Degeneration - drug therapy Macular Degeneration - metabolism Macular Degeneration - prevention & control Mice Neuroprotective Agents - pharmacology Photoreceptor Cells, Vertebrate - drug effects Photoreceptor Cells, Vertebrate - metabolism Research Paper Retinoids - antagonists & inhibitors Retinoids - metabolism Stargardt Disease - drug therapy Stargardt Disease - metabolism Stargardt Disease - prevention & control Treatment Outcome |
| title | Systemic administration of the di-apocarotenoid norbixin (BIO201) is neuroprotective, preserves photoreceptor function and inhibits A2E and lipofuscin accumulation in animal models of age-related macular degeneration and Stargardt disease |
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