title: Calcitriol is a potent inhibitor of retinal neovascularization.
abstract: OBJECTIVE
  Vitamin D compounds inhibit the growth of a variety of tumors in preclinical and clinical studies. Among the mechanisms suggested for this inhibition is antiangiogenesis. Retinal angiogenesis is the basis for vision loss in several major blinding diseases. The purpose of this study was to evaluate the antiangiogenic activity of calcitriol (1,25-dihydroxyvitamin D(3)) in vivo and its effect on retinal endothelial cell (EC) proliferation, migration, and capillary morphogenesis in vitro.
  
  
  METHODS
  The mouse oxygen-induced ischemic retinopathy (OIR) model was used to assess the antiangiogenic activity of calcitriol. Ocular VEGF levels were determined by Western blot analysis of whole eye extracts from postnatal day (P) 15 mice during OIR. The effects of calcitriol on retinal EC proliferation, migration, and capillary morphogenesis were also assessed in vitro.
  
  
  RESULTS
  Calcitriol-treated animals demonstrated a significant decrease in retinal neovascularization compared with control animals. This effect was dose dependent, and retinal neovascularization was significantly inhibited in calcitriol-treated mice. Although no deaths occurred, calcitriol administration was associated with increased serum calcium and a lack of increase in body weight in a dose-independent manner. The ocular level of VEGF was similar in control and calcitriol-treated animals. At a lower concentration of calcitriol, retinal EC capillary morphogenesis in solubilized basement membrane was inhibited without a significant inhibitory effect on EC proliferation and migration. The concentration of calcitriol required to inhibit retinal EC proliferation was significantly higher than that required to inhibit EC capillary morphogenesis.
  
  
  CONCLUSIONS
  These data suggest calcitriol is a potent inhibitor of retinal neovascularization and may be of benefit in the treatment of a variety of eye diseases with a neovascular component.
authors: Departments of Ophthalmology and Visual Sciences, University of Wisconsin Medical School, Madison, Wisconsin 53792-4673, USA.
authors: Daniel M
authors: DM
authors: Albert
authors: Elizabeth A
authors: EA
authors: Scheef
authors: Shoujian
authors: S
authors: Wang
authors: Farideh
authors: F
authors: Mehraein
authors: Soesiawati R
authors: SR
authors: Darjatmoko
authors: Christine M
authors: CM
authors: Sorenson
authors: Nader
authors: N
authors: Sheibani
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D002117:Calcitriol / Q000627:therapeutic use*; D002118:Calcium / Q000097:blood; D002196:Capillaries; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D009024:Morphogenesis / Q000187:drug effects; D015861:Retinal Neovascularization / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D012171:Retinal Vessels / Q000187:drug effects / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014815:Vitamins / Q000627:therapeutic use*
chemical_list: D020533:Angiogenesis Inhibitors; D042461:Vascular Endothelial Growth Factor A; D014815:Vitamins; C467480:vascular endothelial growth factor A, mouse; D002117:Calcitriol; D002118:Calcium