{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T22:27:29Z","timestamp":1791844049783,"version":"4.3.4"},"reference-count":34,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2024,8,9]],"date-time":"2024-08-09T00:00:00Z","timestamp":1723161600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82371098"],"award-info":[{"award-number":["82371098"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2024,8,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The ciliary muscle constitutes a crucial element in refractive regulation. Investigating the pathophysiological mechanisms within the ciliary muscle during excessive contraction holds significance in treating ciliary muscle dysfunction. A guinea pig model of excessive contraction of the ciliary muscle induced by drops pilocarpine was employed, alongside the primary ciliary muscle cells was employed in in\u00a0vitro experiments. The results of the ophthalmic examination showed that pilocarpine did not significantly change refraction and axial length during the experiment, but had adverse effects on the regulatory power of the ciliary muscle. The current data reveal notable alterations in the expression profiles of hypoxia inducible factor 1 (HIF\u20101\u03b1), ATP2A2, P53, \u03b1\u2010SMA, Caspase\u20103, and BAX within the ciliary muscle of animals subjected to pilocarpine exposure, alongside corresponding changes observed in cultured cells treated with pilocarpine. Augmented levels of ROS were detected in both tissue specimens and cells, culminating in a significant increase in cell apoptosis in in\u00a0vivo and in\u00a0vitro experiments. Further examination revealed that pilocarpine induced an increase in intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    levels and disrupted MMP, as evidenced by mitochondrial swelling and diminished cristae density compared to control conditions, concomitant with a noteworthy decline in antioxidant enzyme activity. However, subsequent blockade of Ca\n                    <jats:sup>2+<\/jats:sup>\n                    channels in cells resulted in downregulation of HIF\u20101\u03b1, ATP2A2, P53, \u03b1\u2010SMA, Caspase\u20103, and BAX expression, alongside ameliorated mitochondrial function and morphology. The inhibition of Ca\n                    <jats:sup>2+<\/jats:sup>\n                    channels presents a viable approach to mitigate ciliary cells damage and sustain proper ciliary muscle function by curtailing the mitochondrial damage induced by excessive contractions.\n                  <\/jats:p>","DOI":"10.1096\/fj.202401286r","type":"journal-article","created":{"date-parts":[[2024,8,9]],"date-time":"2024-08-09T09:57:50Z","timestamp":1723197470000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Pilocarpine mediated excessive calcium accumulation leads to ciliary muscle cell senescence and apoptosis"],"prefix":"10.1096","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9660-0742","authenticated-orcid":false,"given":"Xiang","family":"Gao","sequence":"first","affiliation":[{"name":"The First Affiliated Hospital of Chongqing Medical University Chongqing Key Laboratory of Prevention and Treatment 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