Intravitreal Administration of Stanniocalcin-1 Rescues Photoreceptor Degeneration with Reduced Oxidative Stress and Inflammation in a Porcine Model of Retinitis Pigmentosa
To investigate the effect of stanniocalcin-1 (STC-1), a secreted polypeptide exhibiting multiple functions in cell survival and death, on photoreceptor degeneration in a porcine model of retinitis pigmentosa (RP). P23H transgenic pigs (TG P23H) and wild-type hybrid littermates were obtained from the...
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Veröffentlicht in: | American journal of ophthalmology 2022-07, Vol.239, p.230-243 |
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creator | Rosa, Robert H. Xie, Wankun Zhao, Min Tsai, Shu-Huai Roddy, Gavin W. Su, Maxwell G. Potts, Luke B. Hein, Travis W. Kuo, Lih |
description | To investigate the effect of stanniocalcin-1 (STC-1), a secreted polypeptide exhibiting multiple functions in cell survival and death, on photoreceptor degeneration in a porcine model of retinitis pigmentosa (RP).
P23H transgenic pigs (TG P23H) and wild-type hybrid littermates were obtained from the National Swine Resource and Research Center. Human recombinant STC-1 was injected intravitreally every 2 weeks from postnatal day 15 (P15) to P75. The contralateral eye was injected with balanced salt solution as a control. Electroretinography (ERG) and spectral domain optical coherence tomography (SD-OCT) were performed to evaluate retinal function and morphology in vivo at P90. Retinal tissue was collected for histologic analysis and molecular assays to evaluate the antioxidative and anti-inflammatory mechanisms by which STC-1 may rescue photoreceptor degeneration.
Intravitreal injection of STC-1 improved retinal function in TG P23H pigs with increased photopic and flicker ERG a- and b-wave amplitudes. Greater integrity of the ellipsoid zone (EZ) band on SD-OCT and morphologic rescue with preservation of cone photoreceptors were observed in STC-1−treated TG P23H pigs. STC-1 altered gene expression in TG P23H pig retina on microarray analysis and increased photoreceptor specific gene expression by reverse transcription−polymerase chain reaction analysis. STC-1 significantly decreased oxidative stress and the expressions of NLRP3 inflammasome, cleaved caspase-1, and IL-1β in TG P23H pig retina.
Intravitreal administration of STC-1 enhances cone photoreceptor function, improves EZ integrity, and reduces retinal degeneration through antioxidative and anti-inflammatory effects in a large animal (pig) model of the most common form of autosomal dominant RP in the United States. |
doi_str_mv | 10.1016/j.ajo.2022.03.014 |
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P23H transgenic pigs (TG P23H) and wild-type hybrid littermates were obtained from the National Swine Resource and Research Center. Human recombinant STC-1 was injected intravitreally every 2 weeks from postnatal day 15 (P15) to P75. The contralateral eye was injected with balanced salt solution as a control. Electroretinography (ERG) and spectral domain optical coherence tomography (SD-OCT) were performed to evaluate retinal function and morphology in vivo at P90. Retinal tissue was collected for histologic analysis and molecular assays to evaluate the antioxidative and anti-inflammatory mechanisms by which STC-1 may rescue photoreceptor degeneration.
Intravitreal injection of STC-1 improved retinal function in TG P23H pigs with increased photopic and flicker ERG a- and b-wave amplitudes. Greater integrity of the ellipsoid zone (EZ) band on SD-OCT and morphologic rescue with preservation of cone photoreceptors were observed in STC-1−treated TG P23H pigs. STC-1 altered gene expression in TG P23H pig retina on microarray analysis and increased photoreceptor specific gene expression by reverse transcription−polymerase chain reaction analysis. STC-1 significantly decreased oxidative stress and the expressions of NLRP3 inflammasome, cleaved caspase-1, and IL-1β in TG P23H pig retina.
Intravitreal administration of STC-1 enhances cone photoreceptor function, improves EZ integrity, and reduces retinal degeneration through antioxidative and anti-inflammatory effects in a large animal (pig) model of the most common form of autosomal dominant RP in the United States.</description><identifier>ISSN: 0002-9394</identifier><identifier>EISSN: 1879-1891</identifier><identifier>DOI: 10.1016/j.ajo.2022.03.014</identifier><identifier>PMID: 35307380</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Anesthesia ; Angiogenesis ; Animals ; Apoptosis ; Gene expression ; Hogs ; Inflammation ; Mutation ; Optics ; Ovaries ; Oxidative stress ; Photoreceptors ; Proteins ; Tomography</subject><ispartof>American journal of ophthalmology, 2022-07, Vol.239, p.230-243</ispartof><rights>2022 The Authors</rights><rights>Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.</rights><rights>2022. The Authors</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c424t-31084ba27b78c26e91887701745475f28d3c607eb3878dcf8c240701f553c7f23</citedby><cites>FETCH-LOGICAL-c424t-31084ba27b78c26e91887701745475f28d3c607eb3878dcf8c240701f553c7f23</cites><orcidid>0000-0002-1907-8639</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.ajo.2022.03.014$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>315,782,786,3552,27931,27932,46002</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35307380$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rosa, Robert H.</creatorcontrib><creatorcontrib>Xie, Wankun</creatorcontrib><creatorcontrib>Zhao, Min</creatorcontrib><creatorcontrib>Tsai, Shu-Huai</creatorcontrib><creatorcontrib>Roddy, Gavin W.</creatorcontrib><creatorcontrib>Su, Maxwell G.</creatorcontrib><creatorcontrib>Potts, Luke B.</creatorcontrib><creatorcontrib>Hein, Travis W.</creatorcontrib><creatorcontrib>Kuo, Lih</creatorcontrib><title>Intravitreal Administration of Stanniocalcin-1 Rescues Photoreceptor Degeneration with Reduced Oxidative Stress and Inflammation in a Porcine Model of Retinitis Pigmentosa</title><title>American journal of ophthalmology</title><addtitle>Am J Ophthalmol</addtitle><description>To investigate the effect of stanniocalcin-1 (STC-1), a secreted polypeptide exhibiting multiple functions in cell survival and death, on photoreceptor degeneration in a porcine model of retinitis pigmentosa (RP).
P23H transgenic pigs (TG P23H) and wild-type hybrid littermates were obtained from the National Swine Resource and Research Center. Human recombinant STC-1 was injected intravitreally every 2 weeks from postnatal day 15 (P15) to P75. The contralateral eye was injected with balanced salt solution as a control. Electroretinography (ERG) and spectral domain optical coherence tomography (SD-OCT) were performed to evaluate retinal function and morphology in vivo at P90. Retinal tissue was collected for histologic analysis and molecular assays to evaluate the antioxidative and anti-inflammatory mechanisms by which STC-1 may rescue photoreceptor degeneration.
Intravitreal injection of STC-1 improved retinal function in TG P23H pigs with increased photopic and flicker ERG a- and b-wave amplitudes. Greater integrity of the ellipsoid zone (EZ) band on SD-OCT and morphologic rescue with preservation of cone photoreceptors were observed in STC-1−treated TG P23H pigs. STC-1 altered gene expression in TG P23H pig retina on microarray analysis and increased photoreceptor specific gene expression by reverse transcription−polymerase chain reaction analysis. STC-1 significantly decreased oxidative stress and the expressions of NLRP3 inflammasome, cleaved caspase-1, and IL-1β in TG P23H pig retina.
Intravitreal administration of STC-1 enhances cone photoreceptor function, improves EZ integrity, and reduces retinal degeneration through antioxidative and anti-inflammatory effects in a large animal (pig) model of the most common form of autosomal dominant RP in the United States.</description><subject>Anesthesia</subject><subject>Angiogenesis</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Gene expression</subject><subject>Hogs</subject><subject>Inflammation</subject><subject>Mutation</subject><subject>Optics</subject><subject>Ovaries</subject><subject>Oxidative stress</subject><subject>Photoreceptors</subject><subject>Proteins</subject><subject>Tomography</subject><issn>0002-9394</issn><issn>1879-1891</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><recordid>eNp9kU1v1DAQhiMEokvhB3BBlrhwSfBX4kScqvK1UlGrAmfLa09arxJ7sZ0FfhN_klntwoEDp5FnnnlnPG9VPWe0YZR1r7eN2caGU84bKhrK5INqxXo11Kwf2MNqRSnl9SAGeVY9yXmLz05J9bg6E62gSvR0Vf1ah5LM3pcEZiIXbvbBZ8wUHwOJI_lcTAg-WjNZH2pGbiHbBTK5uY8lJrCww0Dewh0EOHV99-UeObdYcOT6h3eY3gMqJciZmODIOoyTmecj7gMx5CYm1AfyKTqYDnNvoeAmxeMkfzdDKDGbp9Wj0UwZnp3iefX1_bsvlx_rq-sP68uLq9pKLkstGO3lxnC1Ub3lHQys75WiTMlWqnbkvRO2owo2ole9syNCkmJ9bFth1cjFefXqqLtL8Rt-tujZZwvTZALEJWveSdYyxumA6Mt_0G1cUsDtkFJtO6hBSqTYkbIp5pxg1LvkZ5N-akb1wUm91eikPjipqdDoJPa8OCkvmxnc344_1iHw5ggAnmLvIelsPQQ8ukdfinbR_0f-N5r6sDI</recordid><startdate>20220701</startdate><enddate>20220701</enddate><creator>Rosa, Robert H.</creator><creator>Xie, Wankun</creator><creator>Zhao, Min</creator><creator>Tsai, Shu-Huai</creator><creator>Roddy, Gavin W.</creator><creator>Su, Maxwell G.</creator><creator>Potts, Luke B.</creator><creator>Hein, Travis W.</creator><creator>Kuo, Lih</creator><general>Elsevier Inc</general><general>Elsevier Limited</general><scope>6I.</scope><scope>AAFTH</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-1907-8639</orcidid></search><sort><creationdate>20220701</creationdate><title>Intravitreal Administration of Stanniocalcin-1 Rescues Photoreceptor Degeneration with Reduced Oxidative Stress and Inflammation in a Porcine Model of Retinitis Pigmentosa</title><author>Rosa, Robert H. ; Xie, Wankun ; Zhao, Min ; Tsai, Shu-Huai ; Roddy, Gavin W. ; Su, Maxwell G. ; Potts, Luke B. ; Hein, Travis W. ; Kuo, Lih</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c424t-31084ba27b78c26e91887701745475f28d3c607eb3878dcf8c240701f553c7f23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Anesthesia</topic><topic>Angiogenesis</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Gene expression</topic><topic>Hogs</topic><topic>Inflammation</topic><topic>Mutation</topic><topic>Optics</topic><topic>Ovaries</topic><topic>Oxidative stress</topic><topic>Photoreceptors</topic><topic>Proteins</topic><topic>Tomography</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rosa, Robert H.</creatorcontrib><creatorcontrib>Xie, Wankun</creatorcontrib><creatorcontrib>Zhao, Min</creatorcontrib><creatorcontrib>Tsai, Shu-Huai</creatorcontrib><creatorcontrib>Roddy, Gavin W.</creatorcontrib><creatorcontrib>Su, Maxwell G.</creatorcontrib><creatorcontrib>Potts, Luke B.</creatorcontrib><creatorcontrib>Hein, Travis W.</creatorcontrib><creatorcontrib>Kuo, Lih</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>American journal of ophthalmology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rosa, Robert H.</au><au>Xie, Wankun</au><au>Zhao, Min</au><au>Tsai, Shu-Huai</au><au>Roddy, Gavin W.</au><au>Su, Maxwell G.</au><au>Potts, Luke B.</au><au>Hein, Travis W.</au><au>Kuo, Lih</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Intravitreal Administration of Stanniocalcin-1 Rescues Photoreceptor Degeneration with Reduced Oxidative Stress and Inflammation in a Porcine Model of Retinitis Pigmentosa</atitle><jtitle>American journal of ophthalmology</jtitle><addtitle>Am J Ophthalmol</addtitle><date>2022-07-01</date><risdate>2022</risdate><volume>239</volume><spage>230</spage><epage>243</epage><pages>230-243</pages><issn>0002-9394</issn><eissn>1879-1891</eissn><abstract>To investigate the effect of stanniocalcin-1 (STC-1), a secreted polypeptide exhibiting multiple functions in cell survival and death, on photoreceptor degeneration in a porcine model of retinitis pigmentosa (RP).
P23H transgenic pigs (TG P23H) and wild-type hybrid littermates were obtained from the National Swine Resource and Research Center. Human recombinant STC-1 was injected intravitreally every 2 weeks from postnatal day 15 (P15) to P75. The contralateral eye was injected with balanced salt solution as a control. Electroretinography (ERG) and spectral domain optical coherence tomography (SD-OCT) were performed to evaluate retinal function and morphology in vivo at P90. Retinal tissue was collected for histologic analysis and molecular assays to evaluate the antioxidative and anti-inflammatory mechanisms by which STC-1 may rescue photoreceptor degeneration.
Intravitreal injection of STC-1 improved retinal function in TG P23H pigs with increased photopic and flicker ERG a- and b-wave amplitudes. Greater integrity of the ellipsoid zone (EZ) band on SD-OCT and morphologic rescue with preservation of cone photoreceptors were observed in STC-1−treated TG P23H pigs. STC-1 altered gene expression in TG P23H pig retina on microarray analysis and increased photoreceptor specific gene expression by reverse transcription−polymerase chain reaction analysis. STC-1 significantly decreased oxidative stress and the expressions of NLRP3 inflammasome, cleaved caspase-1, and IL-1β in TG P23H pig retina.
Intravitreal administration of STC-1 enhances cone photoreceptor function, improves EZ integrity, and reduces retinal degeneration through antioxidative and anti-inflammatory effects in a large animal (pig) model of the most common form of autosomal dominant RP in the United States.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>35307380</pmid><doi>10.1016/j.ajo.2022.03.014</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0002-1907-8639</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Anesthesia Angiogenesis Animals Apoptosis Gene expression Hogs Inflammation Mutation Optics Ovaries Oxidative stress Photoreceptors Proteins Tomography |
title | Intravitreal Administration of Stanniocalcin-1 Rescues Photoreceptor Degeneration with Reduced Oxidative Stress and Inflammation in a Porcine Model of Retinitis Pigmentosa |
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