{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T15:53:30Z","timestamp":1777910010331,"version":"3.51.4"},"reference-count":41,"publisher":"SAGE Publications","issue":"7","license":[{"start":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T00:00:00Z","timestamp":1693526400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Ocular Pharmacology and Therapeutics"],"published-print":{"date-parts":[[2023,9,1]]},"abstract":"<jats:sec>\n                    <jats:title>Purpose:<\/jats:title>\n                    <jats:p>To assess the combined effects of omidenepag (OMD), a selective EP2 agonist, and ripasudil (Rip), an inhibitor of rho-associated coiled-coil containing protein kinases, on the human orbital adipose tissue, two-dimensional (2D) or three-dimensional (3D) cultures of human orbital fibroblasts (HOFs) were employed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      Cellular metabolic functions (2D), physical (3D), lipid staining (3D), and quantitative polymerase chain reaction for adipogenesis-related genes,\n                      <jats:italic toggle=\"yes\">PPAR\u03b3<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">AP2,<\/jats:italic>\n                      and extracellular matrix (ECM) molecules, including collagen\n                      <jats:italic toggle=\"yes\">(COL)1, 4,<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">6<\/jats:italic>\n                      , and fibronectin (\n                      <jats:italic toggle=\"yes\">FN<\/jats:italic>\n                      ) (3D) were evaluated in the presence of OMD (100\u2009nM) and\/or Rip (10\u2009\u03bcM).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Real-time metabolic analyses revealed that the adipogenic differentiation (DIF+) with OMD significantly shifted an energetic state toward energetic, whereas DIF+ with Rip significantly shifted that toward quiescent. In the case of both drugs upon DIF+, the metabolic effect of OMD was predominant. DIF+ induced enlargement and stiffed 3D spheroid with increased lipid staining and mRNA expression of adipogenesis-related genes,\n                      <jats:italic toggle=\"yes\">COL4<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">COL6<\/jats:italic>\n                      , and decreased the expression of\n                      <jats:italic toggle=\"yes\">COL1<\/jats:italic>\n                      . In the presence of OMD and\/or Rip to DIF+, (1) the sizes were further increased by Rip and the stiffness was significantly decreased by OMD or Rip and (2)\n                      <jats:italic toggle=\"yes\">COL4<\/jats:italic>\n                      or\n                      <jats:italic toggle=\"yes\">AP2<\/jats:italic>\n                      expression was substantially increased by OMD or Rip, respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>\n                      The results presented herein indicate that the metabolic effects of OMD and Rip exerted opposing effects and the effects of OMD toward\n                      <jats:italic toggle=\"yes\">Ap2<\/jats:italic>\n                      and ECM expressions were distinct from those of Rip, but the effects of OMD toward the physical aspects and adipogenesis of the 3D cultured HOFs were similar to the effects of Rip.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/jop.2023.0025","type":"journal-article","created":{"date-parts":[[2023,6,23]],"date-time":"2023-06-23T15:57:44Z","timestamp":1687535864000},"page":"439-448","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["Simultaneous Effects of a Selective EP2 Agonist, Omidenepag, and a Rho-Associated Coiled-Coil Containing Protein Kinase Inhibitor, Ripasudil, on Human Orbital Fibroblasts"],"prefix":"10.1177","volume":"39","author":[{"given":"Fumihito","family":"Hikage","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, School of Medicine, Sapporo Medical University, Sapporo, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Megumi","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, School of Medicine, Sapporo Medical 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