VEGF-B inhibits apoptosis via VEGFR-1–mediated suppression of the expression of BH3-only protein genes in mice and rats
J. Clin. Invest. Yang Li, et al. 118:913 doi:10.1172/JCI33673 [Go to this article.]

Figure 3
VEGF-B inhibits axotomy-induced apoptosis in the retina. (A) VEGF-B is highly expressed in the retina as shown by the in situ hybridization assay. A high level of VEGF-B expression was found primarily in the RGCs and the inner and outer nuclear layers (INL and ONL, arrows). VEGFR-1 expression was mainly found in the inner plexiform layer, part of the inner nuclear layer, and the inner and outer segment layers (IS, OS). Scale bar: 50 μm. (B and C) Real-time PCR assay showed that VEGF-B (B) and VEGFR-1 (C) expression were upregulated in the retinae after ONC injury. The upregulation was seen as early as 6 hours after ONC and reached a high level after 1 week. (D–F) A single dose of VEGF-B₁₆₇ intravitreal treatment increased the number of viable RGCs by about 1.7-fold. VEGF-B neutralizing antibody intravitreal treatment decreased the number of viable RGCs by about 33% (F). VEGFR-1 ECD treatment decreased the number of viable RGCs by about 42% (F). Scale bar: 10 μm. (G–J) Real-time PCR analysis revealed that VEGF-B₁₆₇ treatment inhibited the expression of the BH3-only protein genes Noxa (G) and Bmf (H), as well as Bak (I) and p53 (J) expression in both normal and ONC-injured retinae. *P < 0.05, **P < 0.01.