Angiogenesis in response to hypoxia

Angiogenesis is regulated by the balance of angiogenic and anti-angiogenic factors through multiple pathways. In this article, we focus on hypoxia that regulates angiogenic factors. Two potent angiogenic factors - vascular endothelial growth factor (VEGF) and erythropoietin (Epo) - are regulated by transcription factors called hypoxia-inducible factors (HIFs). Several pathways that regulate the HIFs under hypoxic conditions are described. Then, we review the mechanisms, that is, involvement of VEGF and Epo, in pathological angiogenesis in the retina and describe supporting experimental data obtained from model animals, in addition to human clinical data. We also discuss how hypoxia regulates vascular development in the retina.