Figure 1.

Aflibercept induces rapid collapse of mother vessels (MV) to glomeruloid microvascular proliferations (GMP). A–C: Nude mouse ears 6 days after injection of 10⁷ plaque-forming units of adenovirus expressing vascular endothelial growth factor (VEGF)-A (Ad-VEGF-A¹⁶⁴); mice were left untreated or were treated s.c. with a single dose of aflibercept (25 mg/kg) or control peptide 24 hours earlier on day 5. D–R: Light (D–L) and electron (M–R) microscopic images of ears injected 5 days earlier with Ad-VEGF-A¹⁶⁴ and harvested 6 hours after treatment with control peptide (D and M; typical MV) or aflibercept (all others). Transluminal endothelial cell (EC) bridging (E–H, N, and O; black arrows), proceeding to MV collapse and formation of typical GMP (I–L and P–R). Most ECs are healthy with prominent activated nuclei; occasional dead ECs are indicated with yellow shading (K and P–R). Pink shading indicates vascular lumens; red arrows (N), cellular debris within vascular lumens; dashed lines, an MV (D) and GMP formation (F and H–K). n > 50 mice. Scale bars: 10 μm (D–L); 20 μm (M); 5 μm (N and P–R); 1 μm (O). hf, hair follicle.