| PURPOSE. Vitamin D compounds inhibit growth of a variety of tumors in preclinical and clinical studies. Among the mechanisms suggested for this inhibition is anti-angiogenesis. Retinal angiogenesis is the basis for vision loss in several major blinding diseases. Here the antiangiogenic activity of calcitriol (1,25-dihydroxyvitamin D3) in vivo and its effect on retinal endothelial cell (EC) proliferation, migration, and capillary morphogenesis in vitro were evaluated.
METHODS. The mouse oxygen-induced ischemic retinopathy (OIR) model was used to assess the antiangiogenic activity of calcitriol. The ocular VEGF levels were determined by western blot analysis of whole eye extracts from P15 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 to control animals. This effect was dose-dependent and retinal neovascularization was significantly inhibited in calcitriol-treated mice. Although no mortality 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 Matrigel 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 their 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.
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