Vitamin D inhibits angiogenesis in transgenic murine retinoblastoma

Purpose. Vitamin D compounds have been shown to inhibit tumor growth in a transgenic retinoblastoma murine model. The mechanism of action has not been defined clearly, although an antiangiogenic action has been proposed. Methods. Transgenic retinoblastoma mice received high (0.05 μg) and low (0.025 μg) doses of vitamin D3 by intraperitoneal injection 5 times per week for 5 weeks. Control animals were injected with mineral oil vehicle alone. At 5 months of age, the animals were killed and eyes were enucleated and processed for light microscopy. Paraffin-embedded sections were stained with an immunoperoxidase stain (GS-1) specific for mammalian vascular endothelium. Sections were graded by a single masked reviewer, and intraobserver reliability was assessed. Mean vessel counts were made for each group. Results. The high-dose group had the lowest mean vessel count (8.5), followed by the low-dose group (10.1). The control group had the highest mean vessel count (14.1). Vitamin D-treated animals (high- and low-dose groups combined) had significantly fewer vessels (P = 0.001) than untreated controls. Conclusions. These results support the hypothesis that inhibition of angiogenesis is a mechanism of action for vitamin D in the transgenic retinoblastoma mouse model.