Reexpression of annexin A2 restores neoangiogenesis in OIR. (A) RT-PCR of retinal tissue at P14 after subretinal injection of A2-encoding (A2; OD) or empty (V; OS) adenovirus in Anxa2^−/− mice at P12, and immunoblot analysis of identically treated Anxa2^−/− mouse retinas 2 days (P14) after virus injection. The data are representative of 3 independent experiments. (B) Representative retinal images showing total retinal area and regions of NV and VO in oxygen-treated P17 Anxa2^−/− mice injected with either A2-encoding or empty virus on P12. Pixel number corresponding to each compartment is indicated below each image. (C) Ratios of VO to total retinal area (19.5% ± 0.64% vs 19.4% ± 0.79%) and NV to total retinal area (4.7% ± 0.15% vs 8.6% ± 0.12%) in P17 oxygen-treated Anxa2^−/− mice injected with either empty or A2-encoding virus (n = 8; NS indicates no significant difference, ***P < .001). (D) Representative retinal cross-sections (magnification ×40), with a close-up view of the peripheral region (magnification ×200) of retinas from P17 oxygen-treated Anxa2^−/− mice injected with empty or A2-encoding virus stained with DAPI (blue) and isolectin B4 (red). Neovascular tufts penetrating the inner limiting membrane (highlighted with a white dashed line) are indicated by arrowheads. (E) Enumeration of neovascular nuclei in retinal sections from P17 oxygen-treated Anxa2^−/− mice injected with empty versus A2-encoding virus (88 ± 4.2 vs 134 ± 3.5; n = 5; ***P < .001). S indicates sclera; V, vitreous body. Scale bars, 200 μm (B; magnification ×50), 500 μm (D; magnification ×40), 100 μm (D; magnification ×200).