TY - JOUR
T1 - Resveratrol reverses the adverse effects of bevacizumab on cultured ARPE-19 cells
AU - Subramani, Murali
AU - Ponnalagu, Murugeswari
AU - Krishna, Lekshmi
AU - Jeyabalan, Nallathambi
AU - Chevour, Priyanka
AU - Sharma, Anupam
AU - Jayadev, Chaitra
AU - Shetty, Rohit
AU - Begum, Nargis
AU - Archunan, Govindaraju
AU - Das, Debashish
PY - 2017/9/25
Y1 - 2017/9/25
N2 - Age-related macular degeneration (AMD) and proliferative diabetic retinopathy (PDR) are one of the major causes of blindness caused by neo-vascular changes in the retina. Intravitreal anti-VEGF injections are widely used in the treatment of wet-AMD and PDR. A significant percentage of treated patients have complications of repeated injections. Resveratrol (RES) is a polyphenol phytoalexin with anti-oxidative, anti-inflammatory and anti-proliferative properties. Hence, we hypothesized that if RES is used in combination with bevacizumab (BEV, anti-VEGF), it could reverse the adverse effects that precipitate fibrotic changes, drusen formation, tractional retinal detachment and so on. Human retinal pigment epithelial cells were treated with various combinations of BEV and RES. There was partial reduction in secreted VEGF levels compared to untreated controls. Epithelial-mesenchymal transition was lower in BEV + RES treated cultures compared to BEV treated cultures. The proliferation status was similar in BEV + RES as well as BEV treated cultures both groups. Phagocytosis was enhanced in the presence of BEV + RES compared to BEV. Furthermore, we observed that notch signaling was involved in reversing the adverse effects of BEV. This study paves way for a combinatorial strategy to treat as well as prevent adverse effects of therapy in patients with wet AMD and PDR.
AB - Age-related macular degeneration (AMD) and proliferative diabetic retinopathy (PDR) are one of the major causes of blindness caused by neo-vascular changes in the retina. Intravitreal anti-VEGF injections are widely used in the treatment of wet-AMD and PDR. A significant percentage of treated patients have complications of repeated injections. Resveratrol (RES) is a polyphenol phytoalexin with anti-oxidative, anti-inflammatory and anti-proliferative properties. Hence, we hypothesized that if RES is used in combination with bevacizumab (BEV, anti-VEGF), it could reverse the adverse effects that precipitate fibrotic changes, drusen formation, tractional retinal detachment and so on. Human retinal pigment epithelial cells were treated with various combinations of BEV and RES. There was partial reduction in secreted VEGF levels compared to untreated controls. Epithelial-mesenchymal transition was lower in BEV + RES treated cultures compared to BEV treated cultures. The proliferation status was similar in BEV + RES as well as BEV treated cultures both groups. Phagocytosis was enhanced in the presence of BEV + RES compared to BEV. Furthermore, we observed that notch signaling was involved in reversing the adverse effects of BEV. This study paves way for a combinatorial strategy to treat as well as prevent adverse effects of therapy in patients with wet AMD and PDR.
KW - PIGMENT EPITHELIAL-CELLS
KW - DIABETIC MACULAR EDEMA
KW - TO-MESENCHYMAL TRANSITION
KW - GROWTH-FACTOR PHARMACOTHERAPY
KW - ACTIVATED POTASSIUM CHANNELS
KW - DIFFERENT OCULAR CELLS
KW - ANTI-VEGF THERAPY
KW - CHOROIDAL NEOVASCULARIZATION
KW - MEDIATED INHIBITION
KW - OXIDATIVE STRESS
U2 - 10.1038/s41598-017-12496-z
DO - 10.1038/s41598-017-12496-z
M3 - Article
C2 - 28947815
SN - 2045-2322
VL - 7
JO - Scientific Reports
JF - Scientific Reports
M1 - 12242
ER -