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 fig) and low (0.025 fxg) 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 endodielium. 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 lowdose group (10.1). The control group had the highest mean vessel count (14.1). Vitamin Dtreated 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. Invest OphthalmolVisSci. 1995; 36:83-87. .Human retinoblastoma requires the presence of blood vessels to support tumor growth. Retinoblastoma cells grow in a uniform, collar-like pattern around blood vessels with necrosis at a constant radius around blood vessels. 1 It is not known whether the angiogenic stimulus is derived from tumor cells themselves or from ischemic retina. Cultured retinoblastoma cell lines, however, have been shown to produce tumor angiogenesis factors. 2 The natural progression of transgenic murine retinoblastoma indicates that tu