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.
Professor Sergienko Eye Clinic, 47 A Pirogova Street, 21008 Vinnycia, Ukraine ; Department of Ophthalmology, Faculty of Medicine, Albert Szent-Györgyi Clinical Center, University of Szeged, Korányi fasor Ulica 10-11, 6720 Szeged, Hungary ; Stem Cells and Eye Research Laboratory, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Egyetem Téren 1, 4032 Debrecen, Hungary.
Lyubomyr
L
Lytvynchuk
Professor Sergienko Eye Clinic, 47 A Pirogova Street, 21008 Vinnycia, Ukraine.
Andrii
A
Sergienko
State Institution "Research Center for Radiation Medicine of Academy of Medical Sciences of Ukraine", Laboratory of Cell Radiobiology, 53 Melnykova Street, 04050 Kyiv, Ukraine.
Galina
G
Lavrenchuk
Department of Ophthalmology, Faculty of Medicine, Albert Szent-Györgyi Clinical Center, University of Szeged, Korányi fasor Ulica 10-11, 6720 Szeged, Hungary ; Stem Cells and Eye Research Laboratory, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Egyetem Téren 1, 4032 Debrecen, Hungary.
Goran
G
Petrovski