Fig. 1: ATF4–CHOP–GADD34 is induced in TM cells/tissues of human and mouse glaucoma.
From: ATF4 leads to glaucoma by promoting protein synthesis and ER client protein load
a and b Cellular lysates from age-matched normal and glaucomatous primary human TM cells were examined for ER stress markers using Western blotting a and analyzed by densitometric analysis b. The average from two independent experiments is shown graphically (n = 3 cell strains for ATF4 and CHOP; n = 6 cell strains for GADD34; n = 4 cell strains for XBP-1; data are presented as mean ± SEM, 2-tailed unpaired t-test). c and d Representative immunostaining for ATF4 and GADD34 c and its intensity measurements d in age-matched normal and glaucoma donor eyes shows significantly increased ATF4 and GADD34 in glaucomatous TM tissues. Arrow shows TM. SC Schlemm’s canal. Scale bar is 100 µm (n = 9 normal and 11 glaucoma eyes, data are presented as mean ± SEM, two-tailed unpaired t-test). *Indicates fold in section (artifact). e Periocular Dex injections elevate IOP significantly in C57BL/6J mice. 3 months old C57BL/6J mice received vehicle or Dex (200 µg/eye) via periocular conjunctival fornix injections bilaterally every week up to 5 weeks and night IOPs were monitored weekly using rebound tonometry (n = 8 in each group; data are presented as mean ± SEM, two-way ANOVA, ***P < 0.001). f and g Western blot for ER stress markers f and its densitometric analyses g of anterior segment tissues from vehicle and Dex-treated mice demonstrated that induction of chronic ER stress markers is associated with Dex-induced ocular hypertension (n = 3 in each group, data are presented as mean ± SEM, two-tailed unpaired t-test).
