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Each group was killed at 5, 24 and 72\u00a0hr, respectively, following uniocular instillation of 0.05\u00a0ml of 1% atropine. Tissues were sampled after enucleation: conjunctiva, sclera, cornea, iris, ciliary body, lens, retina, aqueous, and vitreous humors. The assay for atropine was performed using liquid chromatography\u2010mass spectrometry (\n                      <jats:styled-content style=\"fixed-case\">LC<\/jats:styled-content>\n                      \u2010\n                      <jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content>\n                      ), and molecular tissue distribution was illustrated using matrix\u2010assisted laser desorption ionization\u2010imaging mass spectrometry (\n                      <jats:styled-content style=\"fixed-case\">MALDI<\/jats:styled-content>\n                      \u2010\n                      <jats:styled-content style=\"fixed-case\">IMS<\/jats:styled-content>\n                      ) via an independent experiment on murine eyes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      At 5\u00a0hr, the highest (mean\u00a0\u00b1\u00a0SEM) concentration of atropine was detected in the conjunctiva (19.05\u00a0\u00b1\u00a05.57\u00a0ng\/mg, p\u00a0&lt;\u00a00.05) with a concentration gradient established anteriorly to posteriorly, as supported by\n                      <jats:styled-content style=\"fixed-case\">MALDI<\/jats:styled-content>\n                      \u2010\n                      <jats:styled-content style=\"fixed-case\">IMS<\/jats:styled-content>\n                      . At 24\u00a0hr, preferential binding of atropine to posterior ocular tissues occurred, demonstrating a reversal of the initial concentration gradient. Atropine has good ocular bioavailability with concentrations of two magnitudes higher than its binding affinity in most tissues at 3\u00a0days. Crossing\u2010over of atropine to the untreated eye occurred within 5\u00a0hr post\u2010administration.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Both transcorneal and transconjunctival\u2010scleral routes are key in atropine absorption. Posterior ocular tissues could be important sites of action by atropine in myopic reduction. In uniocular atropine trials, cross\u2010over effects on the placebo eye should be adjusted to enhance results reliability. Combining the use of\n                      <jats:styled-content style=\"fixed-case\">LC<\/jats:styled-content>\n                      \u2010\n                      <jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content>\n                      and\n                      <jats:styled-content style=\"fixed-case\">MALDI<\/jats:styled-content>\n                      \u2010\n                      <jats:styled-content style=\"fixed-case\">IMS<\/jats:styled-content>\n                      can be a viable approach in the study of the ocular pharmacokinetics of atropine.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/aos.13889","type":"journal-article","created":{"date-parts":[[2018,9,27]],"date-time":"2018-09-27T02:33:34Z","timestamp":1538015614000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["The penetration and distribution of topical atropine in animal ocular 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