Resveratrol reverses the adverse effects of bevacizumab on cultured ARPE-19 cells

Murali Subramani, Murugeswari Ponnalagu, Lekshmi Krishna, Nallathambi Jeyabalan, Priyanka Chevour, Anupam Sharma, Chaitra Jayadev, Rohit Shetty, Nargis Begum, Govindaraju Archunan, Debashish Das*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.

Original languageEnglish
Article number12242
Number of pages16
JournalScientific Reports
Volume7
DOIs
Publication statusPublished - 25 Sept 2017

Keywords

  • PIGMENT EPITHELIAL-CELLS
  • DIABETIC MACULAR EDEMA
  • TO-MESENCHYMAL TRANSITION
  • GROWTH-FACTOR PHARMACOTHERAPY
  • ACTIVATED POTASSIUM CHANNELS
  • DIFFERENT OCULAR CELLS
  • ANTI-VEGF THERAPY
  • CHOROIDAL NEOVASCULARIZATION
  • MEDIATED INHIBITION
  • OXIDATIVE STRESS

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