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. 2013 Sep 3;54(9):5995–6002. doi: 10.1167/iovs.13-12117

Figure 4.

Figure 4

Hypoxia induces modulation of the expression in UPR-associated and vascularization-related genes in ATF4+/− retinas. The relative gene expression was articulated in RQs and was analyzed in C57BL/6 OIR (n = 4) and ATF4+/− OIR (n = 4) retinas at P12, P13, and P15 using a ratio of RQs in experimental groups to RQs in controls. Two-way ANOVA was used to calculate the difference between groups. Compared with C57BL/6 OIR, the ATF4+/− OIR mice experienced induction of the UPR at a much lower level. The level of Atf6 and Bip gene expression was significantly reduced by 50% at P12. Hif1 expression was diminished by almost 60% in ATF4+/− OIR retinas, despite the fact that in naive ATF4+/− animals Hif1a expression was elevated at P12. The level of Flt1 was also significantly reduced by 55% in P12 ATF4+/− OIR retinas, which was in agreement with a greater than 60% reduction of Vegfa gene expression at the same time point. This could perhaps be responsible for the significant downregulation of Tgfb1 (60%) in ATF4-deficient retinas at P15 (*P < 0.05, **P < 0.01, ***P < 0.001, **** P < 0.0001).