**3. RPE vascular response in neovascular AMD**

Response to complement and oxidative stress represent the two major pathways by which the RPE secretes VEGF-A [10–12]. Oxidative stress is the oxidation of cellular macromolecules and complement system, if left unregulated, can directly damage host tissue and recruit immune cells to the vicinity of active complement activation. Also these stresses may act inducing complement-induced RPE secretion of VEGF-A and other vasculogenic molecules in response to oxidative stress and activated complement [13]. However, it is important to emphasize as RPE not be only source of proangiogenic factors, the latter ones could originate from various immune cells or other cell types but RPE is a central player in CNV developing by two important step: (1) the potential for multiple distinct stresses to converge to produce a common (proangiogenic) effect and (2) the diversity of response molecules produced by the RPE that could drive angiogenesis.
