MALDI imaging mass spectrometry revealed atropine distribution in the ocular tissues and its transit from anterior to posterior regions in the whole-eye of rabbit after topical administration
It is essential to elucidate drug distribution in the ocular tissues and drug transit in the eye for ophthalmic pharmaceutical manufacturers. Atropine is a reversible muscarinic receptor used to treat various diseases. However, its distribution in ocular tissues is still incompletely understood. Mat...
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description | It is essential to elucidate drug distribution in the ocular tissues and drug transit in the eye for ophthalmic pharmaceutical manufacturers. Atropine is a reversible muscarinic receptor used to treat various diseases. However, its distribution in ocular tissues is still incompletely understood. Matrix-assisted laser desorption/ionization-imaging mass spectrometry (MALDI-IMS) evaluates drug distribution in biological samples. However, there have been few investigations of drug distribution in ocular tissues, including whole-eye segments. In the present study, we explored the spatial distribution of atropine in the whole-eye segment by MALDI-IMS, and then evaluated the changes in atropine level along the anterior-posterior and superior-inferior axes. A 1% atropine solution was administered to a rabbit and after 30 min, its eye was enucleated, sectioned, and analyzed by MALDI-IMS. Atropine accumulated primarily in the tear menisci but was found at substantially lower concentrations in the tissue surrounding the conjunctival sacs. Relative differences in atropine levels between the anterior and posterior regions provided insights into the post-instillation behavior of atropine. Atropine signal intensities differed among corneal layers and between the superior and inferior eyeball regions. Differences in signal intensity among tissues indicated that the drug migrated to the posterior regions via a periocular-scleral route. Line scan analysis elucidated atropine transit from the anterior to the posterior region. This information is useful for atropine delivery in the ocular tissues and indicates that MALDI-IMS is effective for revealing drug distribution in whole-eye sections. |
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Atropine is a reversible muscarinic receptor used to treat various diseases. However, its distribution in ocular tissues is still incompletely understood. Matrix-assisted laser desorption/ionization-imaging mass spectrometry (MALDI-IMS) evaluates drug distribution in biological samples. However, there have been few investigations of drug distribution in ocular tissues, including whole-eye segments. In the present study, we explored the spatial distribution of atropine in the whole-eye segment by MALDI-IMS, and then evaluated the changes in atropine level along the anterior-posterior and superior-inferior axes. A 1% atropine solution was administered to a rabbit and after 30 min, its eye was enucleated, sectioned, and analyzed by MALDI-IMS. Atropine accumulated primarily in the tear menisci but was found at substantially lower concentrations in the tissue surrounding the conjunctival sacs. Relative differences in atropine levels between the anterior and posterior regions provided insights into the post-instillation behavior of atropine. Atropine signal intensities differed among corneal layers and between the superior and inferior eyeball regions. Differences in signal intensity among tissues indicated that the drug migrated to the posterior regions via a periocular-scleral route. Line scan analysis elucidated atropine transit from the anterior to the posterior region. This information is useful for atropine delivery in the ocular tissues and indicates that MALDI-IMS is effective for revealing drug distribution in whole-eye sections.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0211376</identifier><identifier>PMID: 30682156</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Acetylcholine receptors (muscarinic) ; Administration, Topical ; Animals ; Atropine ; Atropine - analysis ; Atropine - metabolism ; Biological properties ; Biological samples ; Biology and Life Sciences ; Chromatography ; Chromatography, High Pressure Liquid ; Cornea ; Dosage and administration ; Drugs ; Eye ; Eye - chemistry ; Eye - metabolism ; Eye - pathology ; Health aspects ; Ionization ; Ions ; Laboratories ; Liquid chromatography ; Macular degeneration ; Male ; Mass spectrometry ; Mass spectroscopy ; Medicine ; Medicine and Health Sciences ; Menisci ; Metabolites ; Pharmaceuticals ; Photonics ; Physical Sciences ; Physiological aspects ; R&D ; Rabbits ; Research & development ; Research and Analysis Methods ; Scientific imaging ; Spatial distribution ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Spectroscopy ; Tissue Distribution ; Tissues ; Transit</subject><ispartof>PloS one, 2019-01, Vol.14 (1), p.e0211376</ispartof><rights>COPYRIGHT 2019 Public Library of Science</rights><rights>2019 Mori et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2019 Mori et al 2019 Mori et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-ec9750b9305bf3a6838abdd94c2ae801fb94e18e750690995c5ae5a5cfcb25703</citedby><cites>FETCH-LOGICAL-c758t-ec9750b9305bf3a6838abdd94c2ae801fb94e18e750690995c5ae5a5cfcb25703</cites><orcidid>0000-0001-6454-0418</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/PMC6347209/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6347209/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30682156$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Lomonaco, Tommaso</contributor><creatorcontrib>Mori, Naoto</creatorcontrib><creatorcontrib>Mochizuki, Takaharu</creatorcontrib><creatorcontrib>Yamazaki, Fumiyoshi</creatorcontrib><creatorcontrib>Takei, Shiro</creatorcontrib><creatorcontrib>Mano, Hidetoshi</creatorcontrib><creatorcontrib>Matsugi, Takeshi</creatorcontrib><creatorcontrib>Setou, Mitsutoshi</creatorcontrib><title>MALDI imaging mass spectrometry revealed atropine distribution in the ocular tissues and its transit from anterior to posterior regions in the whole-eye of rabbit after topical administration</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>It is essential to elucidate drug distribution in the ocular tissues and drug transit in the eye for ophthalmic pharmaceutical manufacturers. Atropine is a reversible muscarinic receptor used to treat various diseases. However, its distribution in ocular tissues is still incompletely understood. Matrix-assisted laser desorption/ionization-imaging mass spectrometry (MALDI-IMS) evaluates drug distribution in biological samples. However, there have been few investigations of drug distribution in ocular tissues, including whole-eye segments. In the present study, we explored the spatial distribution of atropine in the whole-eye segment by MALDI-IMS, and then evaluated the changes in atropine level along the anterior-posterior and superior-inferior axes. A 1% atropine solution was administered to a rabbit and after 30 min, its eye was enucleated, sectioned, and analyzed by MALDI-IMS. Atropine accumulated primarily in the tear menisci but was found at substantially lower concentrations in the tissue surrounding the conjunctival sacs. Relative differences in atropine levels between the anterior and posterior regions provided insights into the post-instillation behavior of atropine. Atropine signal intensities differed among corneal layers and between the superior and inferior eyeball regions. Differences in signal intensity among tissues indicated that the drug migrated to the posterior regions via a periocular-scleral route. Line scan analysis elucidated atropine transit from the anterior to the posterior region. 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imaging mass spectrometry revealed atropine distribution in the ocular tissues and its transit from anterior to posterior regions in the whole-eye of rabbit after topical administration</title><author>Mori, Naoto ; Mochizuki, Takaharu ; Yamazaki, Fumiyoshi ; Takei, Shiro ; Mano, Hidetoshi ; Matsugi, Takeshi ; Setou, Mitsutoshi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c758t-ec9750b9305bf3a6838abdd94c2ae801fb94e18e750690995c5ae5a5cfcb25703</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Acetylcholine receptors (muscarinic)</topic><topic>Administration, Topical</topic><topic>Animals</topic><topic>Atropine</topic><topic>Atropine - analysis</topic><topic>Atropine - metabolism</topic><topic>Biological properties</topic><topic>Biological samples</topic><topic>Biology and Life Sciences</topic><topic>Chromatography</topic><topic>Chromatography, High Pressure 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distribution in the ocular tissues and drug transit in the eye for ophthalmic pharmaceutical manufacturers. Atropine is a reversible muscarinic receptor used to treat various diseases. However, its distribution in ocular tissues is still incompletely understood. Matrix-assisted laser desorption/ionization-imaging mass spectrometry (MALDI-IMS) evaluates drug distribution in biological samples. However, there have been few investigations of drug distribution in ocular tissues, including whole-eye segments. In the present study, we explored the spatial distribution of atropine in the whole-eye segment by MALDI-IMS, and then evaluated the changes in atropine level along the anterior-posterior and superior-inferior axes. A 1% atropine solution was administered to a rabbit and after 30 min, its eye was enucleated, sectioned, and analyzed by MALDI-IMS. Atropine accumulated primarily in the tear menisci but was found at substantially lower concentrations in the tissue surrounding the conjunctival sacs. Relative differences in atropine levels between the anterior and posterior regions provided insights into the post-instillation behavior of atropine. Atropine signal intensities differed among corneal layers and between the superior and inferior eyeball regions. Differences in signal intensity among tissues indicated that the drug migrated to the posterior regions via a periocular-scleral route. Line scan analysis elucidated atropine transit from the anterior to the posterior region. This information is useful for atropine delivery in the ocular tissues and indicates that MALDI-IMS is effective for revealing drug distribution in whole-eye sections.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>30682156</pmid><doi>10.1371/journal.pone.0211376</doi><tpages>e0211376</tpages><orcidid>https://orcid.org/0000-0001-6454-0418</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Acetylcholine receptors (muscarinic) Administration, Topical Animals Atropine Atropine - analysis Atropine - metabolism Biological properties Biological samples Biology and Life Sciences Chromatography Chromatography, High Pressure Liquid Cornea Dosage and administration Drugs Eye Eye - chemistry Eye - metabolism Eye - pathology Health aspects Ionization Ions Laboratories Liquid chromatography Macular degeneration Male Mass spectrometry Mass spectroscopy Medicine Medicine and Health Sciences Menisci Metabolites Pharmaceuticals Photonics Physical Sciences Physiological aspects R&D Rabbits Research & development Research and Analysis Methods Scientific imaging Spatial distribution Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization Spectroscopy Tissue Distribution Tissues Transit |
title | MALDI imaging mass spectrometry revealed atropine distribution in the ocular tissues and its transit from anterior to posterior regions in the whole-eye of rabbit after topical administration |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-06T07%3A52%3A51IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=MALDI%20imaging%20mass%20spectrometry%20revealed%20atropine%20distribution%20in%20the%20ocular%20tissues%20and%20its%20transit%20from%20anterior%20to%20posterior%20regions%20in%20the%20whole-eye%20of%20rabbit%20after%20topical%20administration&rft.jtitle=PloS%20one&rft.au=Mori,%20Naoto&rft.date=2019-01-25&rft.volume=14&rft.issue=1&rft.spage=e0211376&rft.pages=e0211376-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0211376&rft_dat=%3Cgale_plos_%3EA571057206%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2171190437&rft_id=info:pmid/30682156&rft_galeid=A571057206&rft_doaj_id=oai_doaj_org_article_3892cd948d8040a6a250d478a67eb7b9&rfr_iscdi=true |