Figure 2

Inhibitory effects of topically administered nalfurafine on the expression of angiogenic factors in the naïve cornea. Eye drops containing the kappa opioid receptor agonist nalfurafine were administered topically (0.1 µg/2 μL/eye) once or twice a day to the naïve cornea of BALB/c mice for 14 days. Relative mRNA expression levels of angiogenic factors in the control and treated naïve corneal samples were analyzed by RT-qPCR. (a–f) Significant decreases in mRNA levels were noted at 14 days post treatment in samples that were exposed to nalfurafine once and/or twice a day for the following VEGF signaling components: Vegfa (a), Vegfc (b), Flt1 (c), Kdr (d), Flt4 (e), and Nrp1 (f). Data are presented as the mean ± standard error of the mean (n = 3 in all cases). Statistical significance of differences is illustrated as follows: *P < 0.05; **P < 0.01; ***P < 0.001 (one-way analysis of variance followed by the Bonferroni test). (g) Heatmap shows relative decreases in expression levels of angiogenic factors in the naïve cornea depending on the dosage of nalfurafine. ns, no significant difference.