Proteasome Inhibitor Bortezomib Suppresses Nuclear Factor-Kappa B Activation and Ameliorates Eye Inflammation in Experimental Autoimmune Uveitis

Figure 1

Effect of bortezomib on clinical course of EAU induced with IRBP. (a) Comparison of clinical scores of EAU mice treated with high-dose (0.75 mg/kg) bortezomib (red line, ), low-dose (0.15 mg/kg) bortezomib (black line, ), or PBS (blue line, ) in 0.1 mL. Data shown are the mean clinical score (ordinate) of each experiment group over time (abscissa) and the sum of three independent experiments. Comparison of (the course of the clinical symptoms) high-dose bortezomib-treated EAU mice (blue line) with saline-treated mice (red line) shows a significant difference and is indicated as . Comparison of high-dose bortezomib-treated (blue line) with low-dose bortezomib-treated (black line) EAU mice also shows a significant difference and is indicated as . , via the Wilcoxon signed-rank test. (b), (c), (d), and (e): photomicrographs of H&E stained retinal tissue. Representative photomicrographs of paraffin-fixed H&E stained slides of the retina of (b): naïve C57BL/6 mice without EAU induction, (c): EAU mice that received 0.1 mL PBS treatment (indicates leukocytes in vitreous cavity; indicates retinal folds), (d): EAU mice that received low-dose (0.15 mg/kg) bortezomib treatment, and (e): EAU mice that received high-dose (0.75 mg/kg) bortezomib treatment. The experiment was repeated three times with similar results. GCL: ganglion cell layer. INL: inner nuclear layer. ONL: outer nuclear layer. (f) Average clinical score over time of EAU in mice with high-dose (0.75 mg/kg) bortezomib (blue line, ), etanercept (5 mg/kg) (black line, ), or saline (0.1 mL/mouse) treatment (red line, ). Data shown are the mean clinical score (ordinate) of each experiment group over time (abscissa) and the sum of two independent experiments. , via the Wilcoxon signed-rank test.

(a)

(b) Naïve mice

(c) EAU with saline

(d) EAU with Vel (L)

(e) EAU with Vel (H)

(f)