SHIVA-1 - IN-VITRO AND IN-VIVO TESTS OF THE EFFECTS OF A NOVEL, SYNTHETIC, LYTIC PEPTIDE ON OCULAR CELLS

An investigation was undertaken to determine the toxicity of an intrav itreal injection of a novel peptide drug, Shiva-1, in rabbits. The dru g, a synthetic peptide modeled after lytic peptides secreted by certai n insects, has antiproliferative and antibacterial properties. Initial in vitro experiments showed that the drug, at a concentration of 100 mu M, was toxic to both Y-79 retinoblastoma cells and human retinal pi gment epithelial cells. A wide range of doses (6-1200 mu g) was inject ed into the rabbit vitreous in an attempt to determine the maximum tol erated dose. Retinal toxicity was evaluated clinically, by electroreti nography, and by light microscopy. Some localized toxicity was evident as 200 mu g; all doses of 240 mu g and above wee toxic. While the dru g appears to exhibit a narrow range between effective and toxic doses, the results suggest that this and other peptides of similar design me rit further investigation for the treatment of proliferative and infec tious diseases of the eye.