A Novel Topical Ophthalmic Formulation to Mitigate Acute Mustard Gas Keratopathy In Vivo: A Pilot Study
This pilot study investigated the in vivo therapeutic potential and tolerability of a multimodal ophthalmic formulation, topical eye drops (TED), for acute mustard gas keratopathy (MGK) using a rabbit model. Twenty New Zealand White rabbits were used. Only right eyes of 18 rabbits (oculus dexter [OD...
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creator | Tripathi, Ratnakar Balne, Praveen K Sinha, Nishant R Martin, Lynn M Kamil, Sabeeh Landreneau, James R Gupta, Suneel Rodier, Jason T Sinha, Prashant R Hesemann, Nathan P Hofmann, Alexandria C Fink, Michael K Chaurasia, Shyam S Mohan, Rajiv R |
description | This pilot study investigated the in vivo therapeutic potential and tolerability of a multimodal ophthalmic formulation, topical eye drops (TED), for acute mustard gas keratopathy (MGK) using a rabbit model.
Twenty New Zealand White rabbits were used. Only right eyes of 18 rabbits (oculus dexter [OD]) received single sulfur mustard gas (SM) vapor injury, whereas contralateral eyes were left untreated or received TED for tolerabilty evaluation. Two rabbit eyes received no treatment and served as age-matched naive control. The four groups were: Naive (oculus sinister [OS] untreated eyes; n = 9); TED (OS treated only with TED BID for 3 days; n = 9); SM (OD exposed to SM vapor; n = 9); and SM+TED (OD exposed to SM+TED BID for 3 days; n = 9). Ocular examination in live rabbits were performed utilizing slit-lamp biomicroscopy, Fantes grading system, fluorescein staining, Schirmer's tests, pachymetry, and applanation tonometry. Cellular and molecular changes in rabbit corneas were assessed after humane euthanasia on day-3 and day-7 with histopathological and real-time polymerase chain reaction PCR techniques.
TED to rabbit eyes was found tolerable in vivo. SM-exposed eyes showed significant increase in Fantes scores, central corneal thickness (CCT), Schirmer's test, epithelium-stroma separation, and corneal edema. TED mitigated clinical symptoms by reducing corneal edema, Fantes scores, CCT, and Schirmer's test. Further, TED decreased SM-induced corneal haze, inflammatory and profibrotic markers, transforming growth factor-TGF-β1 and cyclooxygenase-2COX-2, and damage to corneal structure, including epithelial-stromal integrity.
The developed multimodal eyedrop formulation, TED, has potential to mitigate acute MGK effectively in vivo.
TED is effective against MGK. |
doi_str_mv | 10.1167/tvst.9.12.6 |
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Twenty New Zealand White rabbits were used. Only right eyes of 18 rabbits (oculus dexter [OD]) received single sulfur mustard gas (SM) vapor injury, whereas contralateral eyes were left untreated or received TED for tolerabilty evaluation. Two rabbit eyes received no treatment and served as age-matched naive control. The four groups were: Naive (oculus sinister [OS] untreated eyes; n = 9); TED (OS treated only with TED BID for 3 days; n = 9); SM (OD exposed to SM vapor; n = 9); and SM+TED (OD exposed to SM+TED BID for 3 days; n = 9). Ocular examination in live rabbits were performed utilizing slit-lamp biomicroscopy, Fantes grading system, fluorescein staining, Schirmer's tests, pachymetry, and applanation tonometry. Cellular and molecular changes in rabbit corneas were assessed after humane euthanasia on day-3 and day-7 with histopathological and real-time polymerase chain reaction PCR techniques.
TED to rabbit eyes was found tolerable in vivo. SM-exposed eyes showed significant increase in Fantes scores, central corneal thickness (CCT), Schirmer's test, epithelium-stroma separation, and corneal edema. TED mitigated clinical symptoms by reducing corneal edema, Fantes scores, CCT, and Schirmer's test. Further, TED decreased SM-induced corneal haze, inflammatory and profibrotic markers, transforming growth factor-TGF-β1 and cyclooxygenase-2COX-2, and damage to corneal structure, including epithelial-stromal integrity.
The developed multimodal eyedrop formulation, TED, has potential to mitigate acute MGK effectively in vivo.
TED is effective against MGK.</description><identifier>ISSN: 2164-2591</identifier><identifier>EISSN: 2164-2591</identifier><identifier>DOI: 10.1167/tvst.9.12.6</identifier><identifier>PMID: 33200047</identifier><language>eng</language><publisher>United States: The Association for Research in Vision and Ophthalmology</publisher><subject>Animals ; Cornea ; Corneal Diseases ; Corneal Edema ; Mustard Gas - toxicity ; Pilot Projects ; Rabbits</subject><ispartof>Translational vision science & technology, 2020-11, Vol.9 (12), p.6-6</ispartof><rights>Copyright 2020 The Authors.</rights><rights>Copyright 2020 The Authors 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c381t-9d81b6195c3ce69284d3d9969912ef4cfff47f8334f59aa6b6a5ba7e352a686a3</citedby><cites>FETCH-LOGICAL-c381t-9d81b6195c3ce69284d3d9969912ef4cfff47f8334f59aa6b6a5ba7e352a686a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7645241/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7645241/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33200047$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tripathi, Ratnakar</creatorcontrib><creatorcontrib>Balne, Praveen K</creatorcontrib><creatorcontrib>Sinha, Nishant R</creatorcontrib><creatorcontrib>Martin, Lynn M</creatorcontrib><creatorcontrib>Kamil, Sabeeh</creatorcontrib><creatorcontrib>Landreneau, James R</creatorcontrib><creatorcontrib>Gupta, Suneel</creatorcontrib><creatorcontrib>Rodier, Jason T</creatorcontrib><creatorcontrib>Sinha, Prashant R</creatorcontrib><creatorcontrib>Hesemann, Nathan P</creatorcontrib><creatorcontrib>Hofmann, Alexandria C</creatorcontrib><creatorcontrib>Fink, Michael K</creatorcontrib><creatorcontrib>Chaurasia, Shyam S</creatorcontrib><creatorcontrib>Mohan, Rajiv R</creatorcontrib><title>A Novel Topical Ophthalmic Formulation to Mitigate Acute Mustard Gas Keratopathy In Vivo: A Pilot Study</title><title>Translational vision science & technology</title><addtitle>Transl Vis Sci Technol</addtitle><description>This pilot study investigated the in vivo therapeutic potential and tolerability of a multimodal ophthalmic formulation, topical eye drops (TED), for acute mustard gas keratopathy (MGK) using a rabbit model.
Twenty New Zealand White rabbits were used. Only right eyes of 18 rabbits (oculus dexter [OD]) received single sulfur mustard gas (SM) vapor injury, whereas contralateral eyes were left untreated or received TED for tolerabilty evaluation. Two rabbit eyes received no treatment and served as age-matched naive control. The four groups were: Naive (oculus sinister [OS] untreated eyes; n = 9); TED (OS treated only with TED BID for 3 days; n = 9); SM (OD exposed to SM vapor; n = 9); and SM+TED (OD exposed to SM+TED BID for 3 days; n = 9). Ocular examination in live rabbits were performed utilizing slit-lamp biomicroscopy, Fantes grading system, fluorescein staining, Schirmer's tests, pachymetry, and applanation tonometry. Cellular and molecular changes in rabbit corneas were assessed after humane euthanasia on day-3 and day-7 with histopathological and real-time polymerase chain reaction PCR techniques.
TED to rabbit eyes was found tolerable in vivo. SM-exposed eyes showed significant increase in Fantes scores, central corneal thickness (CCT), Schirmer's test, epithelium-stroma separation, and corneal edema. TED mitigated clinical symptoms by reducing corneal edema, Fantes scores, CCT, and Schirmer's test. Further, TED decreased SM-induced corneal haze, inflammatory and profibrotic markers, transforming growth factor-TGF-β1 and cyclooxygenase-2COX-2, and damage to corneal structure, including epithelial-stromal integrity.
The developed multimodal eyedrop formulation, TED, has potential to mitigate acute MGK effectively in vivo.
TED is effective against MGK.</description><subject>Animals</subject><subject>Cornea</subject><subject>Corneal Diseases</subject><subject>Corneal Edema</subject><subject>Mustard Gas - toxicity</subject><subject>Pilot Projects</subject><subject>Rabbits</subject><issn>2164-2591</issn><issn>2164-2591</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkctLAzEQxoMoKurJu-QoSGvz2OzGg1CKL2xV8HEN02y2jWQ3a5It9L93iw90DvNgfnwz8CF0TEZDQkR-nlYxDeWQ0KHYQvuUCD6gmSTbf_o9dBTj-6gPUWSci120xxjtR57vo8UYP_iVcfjFt1aDw4_tMi3B1Vbjax_qzkGyvsHJ45lNdgHJ4LHu-jzrYoJQ4huI-N4ESL6FtFzjuwa_2ZW_wGP8ZJ1P-Dl15foQ7VTgojn6rgfo9frqZXI7mD7e3E3G04FmBUkDWRZkLojMNNNGSFrwkpVSCikJNRXXVVXxvCoY41UmAcRcQDaH3LCMgigEsAN0-aXbdvPalNo0KYBTbbA1hLXyYNX_TWOXauFXKhc8o5z0AqffAsF_dCYmVduojXPQGN9FRbkgTEqeix49-0J18DEGU_2eISO1cUdt3FFSEao29Mnfz37ZHy_YJ7BpjI8</recordid><startdate>20201101</startdate><enddate>20201101</enddate><creator>Tripathi, Ratnakar</creator><creator>Balne, Praveen K</creator><creator>Sinha, Nishant R</creator><creator>Martin, Lynn M</creator><creator>Kamil, Sabeeh</creator><creator>Landreneau, James R</creator><creator>Gupta, Suneel</creator><creator>Rodier, Jason T</creator><creator>Sinha, Prashant R</creator><creator>Hesemann, Nathan P</creator><creator>Hofmann, Alexandria C</creator><creator>Fink, Michael K</creator><creator>Chaurasia, Shyam S</creator><creator>Mohan, Rajiv R</creator><general>The Association for Research in Vision and Ophthalmology</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>20201101</creationdate><title>A Novel Topical Ophthalmic Formulation to Mitigate Acute Mustard Gas Keratopathy In Vivo: A Pilot Study</title><author>Tripathi, Ratnakar ; Balne, Praveen K ; Sinha, Nishant R ; Martin, Lynn M ; Kamil, Sabeeh ; Landreneau, James R ; Gupta, Suneel ; Rodier, Jason T ; Sinha, Prashant R ; Hesemann, Nathan P ; Hofmann, Alexandria C ; Fink, Michael K ; Chaurasia, Shyam S ; Mohan, Rajiv R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c381t-9d81b6195c3ce69284d3d9969912ef4cfff47f8334f59aa6b6a5ba7e352a686a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Animals</topic><topic>Cornea</topic><topic>Corneal Diseases</topic><topic>Corneal Edema</topic><topic>Mustard Gas - toxicity</topic><topic>Pilot Projects</topic><topic>Rabbits</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tripathi, Ratnakar</creatorcontrib><creatorcontrib>Balne, Praveen K</creatorcontrib><creatorcontrib>Sinha, Nishant R</creatorcontrib><creatorcontrib>Martin, Lynn M</creatorcontrib><creatorcontrib>Kamil, Sabeeh</creatorcontrib><creatorcontrib>Landreneau, James R</creatorcontrib><creatorcontrib>Gupta, Suneel</creatorcontrib><creatorcontrib>Rodier, Jason T</creatorcontrib><creatorcontrib>Sinha, Prashant R</creatorcontrib><creatorcontrib>Hesemann, Nathan P</creatorcontrib><creatorcontrib>Hofmann, Alexandria C</creatorcontrib><creatorcontrib>Fink, Michael K</creatorcontrib><creatorcontrib>Chaurasia, Shyam S</creatorcontrib><creatorcontrib>Mohan, Rajiv R</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>Translational vision science & technology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tripathi, Ratnakar</au><au>Balne, Praveen K</au><au>Sinha, Nishant R</au><au>Martin, Lynn M</au><au>Kamil, Sabeeh</au><au>Landreneau, James R</au><au>Gupta, Suneel</au><au>Rodier, Jason T</au><au>Sinha, Prashant R</au><au>Hesemann, Nathan P</au><au>Hofmann, Alexandria C</au><au>Fink, Michael K</au><au>Chaurasia, Shyam S</au><au>Mohan, Rajiv R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Novel Topical Ophthalmic Formulation to Mitigate Acute Mustard Gas Keratopathy In Vivo: A Pilot Study</atitle><jtitle>Translational vision science & technology</jtitle><addtitle>Transl Vis Sci Technol</addtitle><date>2020-11-01</date><risdate>2020</risdate><volume>9</volume><issue>12</issue><spage>6</spage><epage>6</epage><pages>6-6</pages><issn>2164-2591</issn><eissn>2164-2591</eissn><abstract>This pilot study investigated the in vivo therapeutic potential and tolerability of a multimodal ophthalmic formulation, topical eye drops (TED), for acute mustard gas keratopathy (MGK) using a rabbit model.
Twenty New Zealand White rabbits were used. Only right eyes of 18 rabbits (oculus dexter [OD]) received single sulfur mustard gas (SM) vapor injury, whereas contralateral eyes were left untreated or received TED for tolerabilty evaluation. Two rabbit eyes received no treatment and served as age-matched naive control. The four groups were: Naive (oculus sinister [OS] untreated eyes; n = 9); TED (OS treated only with TED BID for 3 days; n = 9); SM (OD exposed to SM vapor; n = 9); and SM+TED (OD exposed to SM+TED BID for 3 days; n = 9). Ocular examination in live rabbits were performed utilizing slit-lamp biomicroscopy, Fantes grading system, fluorescein staining, Schirmer's tests, pachymetry, and applanation tonometry. Cellular and molecular changes in rabbit corneas were assessed after humane euthanasia on day-3 and day-7 with histopathological and real-time polymerase chain reaction PCR techniques.
TED to rabbit eyes was found tolerable in vivo. SM-exposed eyes showed significant increase in Fantes scores, central corneal thickness (CCT), Schirmer's test, epithelium-stroma separation, and corneal edema. TED mitigated clinical symptoms by reducing corneal edema, Fantes scores, CCT, and Schirmer's test. Further, TED decreased SM-induced corneal haze, inflammatory and profibrotic markers, transforming growth factor-TGF-β1 and cyclooxygenase-2COX-2, and damage to corneal structure, including epithelial-stromal integrity.
The developed multimodal eyedrop formulation, TED, has potential to mitigate acute MGK effectively in vivo.
TED is effective against MGK.</abstract><cop>United States</cop><pub>The Association for Research in Vision and Ophthalmology</pub><pmid>33200047</pmid><doi>10.1167/tvst.9.12.6</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Animals Cornea Corneal Diseases Corneal Edema Mustard Gas - toxicity Pilot Projects Rabbits |
title | A Novel Topical Ophthalmic Formulation to Mitigate Acute Mustard Gas Keratopathy In Vivo: A Pilot Study |
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