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Our aim was to uncover novel pharmacological regulators of ocular angiogenesis by phenotype\u2010based screening in zebrafish.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>A bioactive chemical library of 465 drugs was screened to identify small molecule inhibitors of ocular hyaloid vasculature (HV) angiogenesis in zebrafish larvae. Selectivity was assessed by evaluation of non\u2010ocular intersegmental vasculature development. Safety pharmacology examined visual behaviour and retinal histology in larvae. Molecular mechanisms of action were scrutinized using expression profiling of target mRNAs and miRNAs in larval eyes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      Library screening identified 10 compounds which significantly inhibited HV developmental angiogenesis. The validated hit calcitriol selectively demonstrated dose\u2010dependent attenuation of HV development. In agreement, vitamin D receptor (VDR) agonists paricalcitol, doxercalciferol, maxacalcitol, calcipotriol, seocalcitol, calcifediol and tacalcitol significantly and selectively attenuated HV development. VDR agonists induced minor ocular morphology abnormalities and affected normal visual function. Calcitriol induced a three to sevenfold increase in ocular dre\u2010miR\u201021 expression. Consistently, all\u2010trans\u2010retinoic acid attenuated HV development and increased ocular dre\u2010miR\u201021 expression. Interestingly, zebrafish ocular\n                      <jats:italic>vegfaa<\/jats:italic>\n                      and\n                      <jats:italic>vegfab<\/jats:italic>\n                      expression was significantly increased while\n                      <jats:italic>, vegfc, flt1<\/jats:italic>\n                      and\n                      <jats:italic>kdrl<\/jats:italic>\n                      expression was unchanged by calcitriol.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Implications<\/jats:title>\n                    <jats:p>These studies identified VDR agonists as significant and selective anti\u2010angiogenics in the developing vertebrate eye and miR21 as a key downstream regulated miRNA. These targets should be further evaluated as molecular hallmarks of, and therapeutic targets for pathological ocular neovascularization.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.13875","type":"journal-article","created":{"date-parts":[[2017,5,26]],"date-time":"2017-05-26T05:02:50Z","timestamp":1495774970000},"page":"2636-2651","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Vitamin D receptor agonists regulate ocular developmental angiogenesis and modulate expression of dre\u2010miR\u201021 and VEGF"],"prefix":"10.1111","volume":"174","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3699-7282","authenticated-orcid":false,"given":"Stephanie L","family":"Merrigan","sequence":"first","affiliation":[{"name":"UCD School of Biomolecular and Biomedical Science UCD Conway Institute, University College Dublin  Dublin 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