Efficacy of Antibody Delivery to the Retina and Optic Nerve by Topical Administration
The purpose of this study was to determine whether nonspecific and ICAM-1-specific IgG1 antibodies can accumulate in the rat retina following topical application, and to develop a model system to show that antibodies that reach the posterior segment retain their pharmacological properties. Eye drops...
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| Veröffentlicht in: | Journal of ocular pharmacology and therapeutics 2016-05, Vol.32 (4), p.203-210 |
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| creator | Hu, Stacy Koevary, Steven |
| description | The purpose of this study was to determine whether nonspecific and ICAM-1-specific IgG1 antibodies can accumulate in the rat retina following topical application, and to develop a model system to show that antibodies that reach the posterior segment retain their pharmacological properties.
Eye drops containing mouse IgG1 or anti-ICAM-1 and the permeation enhancer saponin were topically applied to the eyes of Lewis rats. Concentrations were determined in the retina and optic nerve up to 30 min later using ELISA assays. We also developed an in vitro model to assess the pharmacologic activity of topically delivered antibodies in the retina based on the requirement of human umbilical vein endothelial cells (HUVECs) for vascular endothelial growth factor (VEGF) for growth. Rat eyes were treated with anti-VEGF antibody in the same manner as above; their retinas, harvested shortly thereafter, were added to HUVECs cultured in VEGF-containing media. The effect of these retinal homogenates on HUVEC proliferation was then assessed.
Significant concentrations of IgG1 were detected in the optic nerve (P |
| doi_str_mv | 10.1089/jop.2015.0111 |
| format | Article |
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Eye drops containing mouse IgG1 or anti-ICAM-1 and the permeation enhancer saponin were topically applied to the eyes of Lewis rats. Concentrations were determined in the retina and optic nerve up to 30 min later using ELISA assays. We also developed an in vitro model to assess the pharmacologic activity of topically delivered antibodies in the retina based on the requirement of human umbilical vein endothelial cells (HUVECs) for vascular endothelial growth factor (VEGF) for growth. Rat eyes were treated with anti-VEGF antibody in the same manner as above; their retinas, harvested shortly thereafter, were added to HUVECs cultured in VEGF-containing media. The effect of these retinal homogenates on HUVEC proliferation was then assessed.
Significant concentrations of IgG1 were detected in the optic nerve (P < 0.001) and retina (P < 0.0001) following topical application. Anti-ICAM-1 antibody also accumulated in the retina after topical application, though levels were less than those seen with IgG1 probably owing to a lower starting concentration. Retinal homogenates from eyes treated with anti-VEGF antibody significantly suppressed HUVEC proliferation (P < 0.0001).
Our data support the contention that topically applied antibodies can accumulate in the posterior segment, and suggest they retain their pharmacological properties.</description><identifier>ISSN: 1080-7683</identifier><identifier>EISSN: 1557-7732</identifier><identifier>DOI: 10.1089/jop.2015.0111</identifier><identifier>PMID: 26771217</identifier><language>eng</language><publisher>United States: Mary Ann Liebert, Inc</publisher><subject>Administration, Topical ; Animals ; Cell Proliferation - drug effects ; Female ; Human Umbilical Vein Endothelial Cells - drug effects ; Humans ; Immunoglobulin G - administration & dosage ; Immunoglobulin G - metabolism ; Immunoglobulin G - pharmacology ; Optic Nerve - immunology ; Optic Nerve - metabolism ; Original ; Rats ; Rats, Inbred Lew ; Retina - immunology ; Retina - metabolism</subject><ispartof>Journal of ocular pharmacology and therapeutics, 2016-05, Vol.32 (4), p.203-210</ispartof><rights>Copyright 2016, Mary Ann Liebert, Inc. 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c387t-61860467c7604f0868eedf0ab568e412e21f88fdcd41f4f6461f56629deedde3</citedby><cites>FETCH-LOGICAL-c387t-61860467c7604f0868eedf0ab568e412e21f88fdcd41f4f6461f56629deedde3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26771217$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hu, Stacy</creatorcontrib><creatorcontrib>Koevary, Steven</creatorcontrib><title>Efficacy of Antibody Delivery to the Retina and Optic Nerve by Topical Administration</title><title>Journal of ocular pharmacology and therapeutics</title><addtitle>J Ocul Pharmacol Ther</addtitle><description>The purpose of this study was to determine whether nonspecific and ICAM-1-specific IgG1 antibodies can accumulate in the rat retina following topical application, and to develop a model system to show that antibodies that reach the posterior segment retain their pharmacological properties.
Eye drops containing mouse IgG1 or anti-ICAM-1 and the permeation enhancer saponin were topically applied to the eyes of Lewis rats. Concentrations were determined in the retina and optic nerve up to 30 min later using ELISA assays. We also developed an in vitro model to assess the pharmacologic activity of topically delivered antibodies in the retina based on the requirement of human umbilical vein endothelial cells (HUVECs) for vascular endothelial growth factor (VEGF) for growth. Rat eyes were treated with anti-VEGF antibody in the same manner as above; their retinas, harvested shortly thereafter, were added to HUVECs cultured in VEGF-containing media. The effect of these retinal homogenates on HUVEC proliferation was then assessed.
Significant concentrations of IgG1 were detected in the optic nerve (P < 0.001) and retina (P < 0.0001) following topical application. Anti-ICAM-1 antibody also accumulated in the retina after topical application, though levels were less than those seen with IgG1 probably owing to a lower starting concentration. Retinal homogenates from eyes treated with anti-VEGF antibody significantly suppressed HUVEC proliferation (P < 0.0001).
Our data support the contention that topically applied antibodies can accumulate in the posterior segment, and suggest they retain their pharmacological properties.</description><subject>Administration, Topical</subject><subject>Animals</subject><subject>Cell Proliferation - drug effects</subject><subject>Female</subject><subject>Human Umbilical Vein Endothelial Cells - drug effects</subject><subject>Humans</subject><subject>Immunoglobulin G - administration & dosage</subject><subject>Immunoglobulin G - metabolism</subject><subject>Immunoglobulin G - pharmacology</subject><subject>Optic Nerve - immunology</subject><subject>Optic Nerve - metabolism</subject><subject>Original</subject><subject>Rats</subject><subject>Rats, Inbred Lew</subject><subject>Retina - immunology</subject><subject>Retina - metabolism</subject><issn>1080-7683</issn><issn>1557-7732</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkUlLBDEQhYMo7kevkqOXHlO9JPEiDDouIAoynkMmqWikp9N2MgP9783ggp6qoL56r6hHyAmwCTB5cf4e-knJoJkwANgi-9A0ohCiKrdzzyQrBJfVHjmI8Z0xqBiHXbJXciGgBLFPXmbOeaPNSIOj0y75RbAjvcbWr3EYaQo0vSF9xuQ7TXVn6VOfvKGPOKyRLkY6D31eb-nULn3nYxp08qE7IjtOtxGPv-shmd_M5ld3xcPT7f3V9KEwlRSp4CA5q7kwIhfHJJeI1jG9aHJXQ4klOCmdNbYGVztec3AN5-WFzZzF6pBcfsn2q8USrcEu-7eqH_xSD6MK2qv_k86_qdewVnX25RXLAmffAkP4WGFMaumjwbbVHYZVVCCkqEV-b5nR4gs1Q4hxQPdrA0xtklA5CbVJQm2SyPzp39t-6Z_XV5_T-YWQ</recordid><startdate>201605</startdate><enddate>201605</enddate><creator>Hu, Stacy</creator><creator>Koevary, Steven</creator><general>Mary Ann Liebert, 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><scope>5PM</scope></search><sort><creationdate>201605</creationdate><title>Efficacy of Antibody Delivery to the Retina and Optic Nerve by Topical Administration</title><author>Hu, Stacy ; Koevary, Steven</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c387t-61860467c7604f0868eedf0ab568e412e21f88fdcd41f4f6461f56629deedde3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Administration, Topical</topic><topic>Animals</topic><topic>Cell Proliferation - drug effects</topic><topic>Female</topic><topic>Human Umbilical Vein Endothelial Cells - drug effects</topic><topic>Humans</topic><topic>Immunoglobulin G - administration & dosage</topic><topic>Immunoglobulin G - metabolism</topic><topic>Immunoglobulin G - pharmacology</topic><topic>Optic Nerve - immunology</topic><topic>Optic Nerve - metabolism</topic><topic>Original</topic><topic>Rats</topic><topic>Rats, Inbred Lew</topic><topic>Retina - immunology</topic><topic>Retina - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hu, Stacy</creatorcontrib><creatorcontrib>Koevary, Steven</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><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of ocular pharmacology and therapeutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hu, Stacy</au><au>Koevary, Steven</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Efficacy of Antibody Delivery to the Retina and Optic Nerve by Topical Administration</atitle><jtitle>Journal of ocular pharmacology and therapeutics</jtitle><addtitle>J Ocul Pharmacol Ther</addtitle><date>2016-05</date><risdate>2016</risdate><volume>32</volume><issue>4</issue><spage>203</spage><epage>210</epage><pages>203-210</pages><issn>1080-7683</issn><eissn>1557-7732</eissn><abstract>The purpose of this study was to determine whether nonspecific and ICAM-1-specific IgG1 antibodies can accumulate in the rat retina following topical application, and to develop a model system to show that antibodies that reach the posterior segment retain their pharmacological properties.
Eye drops containing mouse IgG1 or anti-ICAM-1 and the permeation enhancer saponin were topically applied to the eyes of Lewis rats. Concentrations were determined in the retina and optic nerve up to 30 min later using ELISA assays. We also developed an in vitro model to assess the pharmacologic activity of topically delivered antibodies in the retina based on the requirement of human umbilical vein endothelial cells (HUVECs) for vascular endothelial growth factor (VEGF) for growth. Rat eyes were treated with anti-VEGF antibody in the same manner as above; their retinas, harvested shortly thereafter, were added to HUVECs cultured in VEGF-containing media. The effect of these retinal homogenates on HUVEC proliferation was then assessed.
Significant concentrations of IgG1 were detected in the optic nerve (P < 0.001) and retina (P < 0.0001) following topical application. Anti-ICAM-1 antibody also accumulated in the retina after topical application, though levels were less than those seen with IgG1 probably owing to a lower starting concentration. Retinal homogenates from eyes treated with anti-VEGF antibody significantly suppressed HUVEC proliferation (P < 0.0001).
Our data support the contention that topically applied antibodies can accumulate in the posterior segment, and suggest they retain their pharmacological properties.</abstract><cop>United States</cop><pub>Mary Ann Liebert, Inc</pub><pmid>26771217</pmid><doi>10.1089/jop.2015.0111</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1080-7683 |
| ispartof | Journal of ocular pharmacology and therapeutics, 2016-05, Vol.32 (4), p.203-210 |
| issn | 1080-7683 1557-7732 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4860630 |
| source | MEDLINE; Alma/SFX Local Collection |
| subjects | Administration, Topical Animals Cell Proliferation - drug effects Female Human Umbilical Vein Endothelial Cells - drug effects Humans Immunoglobulin G - administration & dosage Immunoglobulin G - metabolism Immunoglobulin G - pharmacology Optic Nerve - immunology Optic Nerve - metabolism Original Rats Rats, Inbred Lew Retina - immunology Retina - metabolism |
| title | Efficacy of Antibody Delivery to the Retina and Optic Nerve by Topical Administration |
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