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. 2021 Jun 15;131(12):e139202. doi: 10.1172/JCI139202

Figure 11. Inhibition of HIF-1α or HIF-2α prevents the development of retinal neovascularization in OIR mice.

Figure 11

(A) Schematic summarizing the time-dependent and cell-specific hypoxic induction of HIF-1α and HIF-2α accumulation in inner retinal cells defines 2 phases of the ischemic stage of the OIR model. In the first phase (P12–P14), the onset of hypoxia (green) corresponded with the rapid accumulation of Hif-1α mRNA (cyan) and protein (blue) expression in retinal glial cells. In the second phase (P14–P17), the rapid accumulation of HIF-2α was observed in the INL (solid purple) and GCL (dashed red lines). This resulted in the accumulation of VEGF expression (orange) and retinal neovascularization (red). (B) Injection (i.p.) with digoxin (2 mg/kg) at P12.5 (designated D1) provided transient (24-hour) pharmacological inhibition of HIF-1α in OIR mice. (C) Retinal neovascularization (outlined) at P17 after inhibition of peak expression of HIF-1α or HIF-2α with a single i.p. injection of digoxin (2 mg/kg) on P12.5 (D1) or P13.5 (designated D2), respectively, compared with vehicle (DMSO) control. (D) Quantitation of avascular retina and retinal neovascularization at P17 after D1 or D2 treatment compared with vehicle control in OIR mice. Data are shown as mean ± SD. Statistical analyses were performed by 1-way ANOVA with Bonferroni’s multiple-comparison test. *P < 0.05; **P < 0.01; ***P < 0.001. P, postnatal; NS, nonsignificant. Scale bar: 500 μm.