Riluzole inhibits VEGF-induced endothelial cell proliferation in vitro and hyperoxia-induced abnormal vessel formation in vivo.

PURPOSE

The present study examined the effects of riluzole, a Food and Drug Administration-approved drug for amyotrophic lateral sclerosis, on VEGF-stimulated endothelial cell proliferation in culture, and on neovascularization in a rat model of retinopathy of prematurity (ROP).

METHODS

Human umbilical vein endothelial cell and bovine retinal endothelial cell cultures were treated with VEGF to induce endothelial cell proliferation in the presence or absence of riluzole. Activation of PKC betaII was examined by quantifying its phosphorylated form on immunoblots. ROP was induced in 5-day-old rat pups by raising them in hyperoxic conditions for 7 days and in normoxic conditions for the next 5 days. Dextran fluorescence retinal angiography was used to quantitatively assess ROP.

RESULTS

Riluzole inhibited VEGF-stimulated PKC betaII activation and cell proliferation in bovine retinal endothelial cell and human umbilical vein endothelial cell cultures. In addition, systemic administration of riluzole substantially ameliorated abnormal new vessel formation in the rat ROP model.

CONCLUSIONS

The present results suggest that riluzole is a potent inhibitor of VEGF-induced endothelial cell proliferation both in vivo and in vitro. Since long-term use of riluzole has already been proven safe in humans, the present data indicate that clinical trials of riluzole for proliferative retinopathies should be implemented expeditiously.