Soluble epoxide hydrolase (sEH) expression and activity are increased and Sar5399 effectively restrains its activity in retinae from PKD rats. (A) sEH (red) and glial fibrillary acidic protein (GFAP, green) expression was assessed by confocal microscopy of retinal cryo-sections (6 µm) from 3 month old Sprague Dawley (SD) and polycystic kidney disease (PKD) rats; bar = 20 µm. On the far left a negative control (Neg) using rabbit IgG was included. ILM: inner limiting membrane. GC, ganglion cell layer; IPL, inner plexiform layer; INL, inner nuclear layer; OPL, outer plexiform layer; ONL, outer nuclear layer; OLM, outer limiting membrane. sEH expression was labeled in red color and particularly observed in IPL and OPL of PKD rats. Comparable results were obtained in retinae from three additional animals. (B) Representative blot and quantification of sEH protein expression in retinae from SD and PKD rats; n = 5; ***P < 0.001 (unpaired t-test, two tailed). (C) Retinal sEH activity (pg diol/µg protein/minute) in retinae from SD and PKD rats treated with vehicle or Sar5399 (sEH-I; 30 mg/kg, 4 weeks); n = 5; **P < 0.01, ***P < 0.001 (two-way ANOVA with Tukey's multiple comparisons test). (D) Chemical structure of Sar5399.