Concerning the safety of PACAP, we reported that PACAP eye drops did not cause any adverse reactions in acute to semi-acute phases of dry eye at a concentration of 100 nM, which is a concentration 1000 times higher than the effective dose of PACAP (0.1 nM), or in response to chronic eye drop treatment at a concentration of 0.1 nM for 3 weeks in PACAP KO mice [63]. The gene discussed is ADCYAP1; the disease is dry eye syndrome.