Fig. 3: Lentiviral expression of ATF4 but not CHOP induces glaucoma in mice.
From: ATF4 leads to glaucoma by promoting protein synthesis and ER client protein load
a Night-time IOP measurements in mice injected intravitreally with lentiviral particles expressing GFP (control), ATF4, and CHOP (2 × 106 TU/eye). A significant IOP elevation was observed in ATF4-injected mice compared to GFP or CHOP-injected mice (n = 7 in GFP group, n = 8 in ATF4 and CHOP groups; data are presented as mean ± SEM, two-way ANOVA, Tukey’s multiple comparison test, ****P < 0.0001). b RGC functional loss in ATF4-injected mice. A decrease in pattern ERG amplitudes was observed in 8 weeks ATF4-injected mice (n = 7) compared to GFP-injected mice (n = 5; data are presented as mean ± SEM, two-tailed unpaired t-test. c Loss of RGCs in 10 weeks ATF4-injected mice. Representative images showing peripheral, mid-peripheral, and central regions of whole mount retinas stained with RBPMS (RGC marker) in GFP (n = 7) and ATF4 (n = 8) injected groups. d RGC counts per 0.393 mm2 of total retina in peripheral, mid-peripheral, and central regions of ATF4 and GFP-injected mice demonstrated significant loss of RGCs in periphery and mid-periphery of ATF4-injected retinas. Scale bar is 50 µm. Data are presented as mean ± SEM, one-way ANOVA; n = 7 for GFP and n = 8 for ATF4. e Representative images of optic nerve sections stained with PPD showing loss of axons in 10 weeks ATF4-injected mice. Scale bar is 10 µm (n = 5 in GFP and n = 5 in ATF4 injected mice). f PPD stained optic nerve axons were counted and total number of axons per optic nerve were shown graphically in GFP (n = 5) vs. ATF4 (n = 5) injected mice groups (data are presented as mean ± SEM, two-tailed unpaired t-test).
