Antiproliferative,Apoptotic,and Autophagic Activity of Ranibizumab,Bevacizumab,Pegaptanib,and Aflibercept on Fibroblasts: Implication for Choroidal Neovascularization

Purpose. choroidal neovascularization (cnv) is one of the most common complications of retinal diseases accompanied by elevated secretion of vascular endothelial growth factor (vegf). intravitreal anti-vegfs (ranibizumab,bevacizumab,pegaptanib,and aflibercept) can suppress neovascularization,decrease vascular permeability and cnv size,and,thereby,improve visual function. the antiproliferative,apoptotic,and autophagic effect of anti-vegf drugs on fibroblasts found in cnvs has not been yet explored. methods. concentration-dependent cellular effects of the four anti-vegfs were examined in l929 fibroblasts over a 5-day period. the cell survival,mitotic and polykaryocytic indices,the level of apoptosis and autophagy,and the cellular growth kinetics were all assessed. results. the anti-vegfs could inhibit the survival,mitotic activity,and proliferation as well as increase the cellular heterogeneity,apoptosis,and autophagy of the fibroblasts in a dose-dependent manner. cellular growth kinetics showed ranibizumab to be less aggressive,but three other anti-vegfs showed higher antiproliferative and apoptotic activity and expressed negative cellular growth kinetics. conclusions. the antiproliferative,apoptotic,and autophagic activity of anti-vegfs upon fibroblasts may explain the cellular response and the etiology of cnv involution in vivo and serve as a good study model for cnv in vitro. © 2015 lyubomyr lytvynchuk et al.