Comparative analysis of bevacizumab and sorafenib on the survival of retinal ganglion cells in the treatment of retinal diseases

Abstract

This study investigates the effects of bevacizumab, a common vascular endothelial growth factor (VEGF) inhibitor, in treating ocular neovascular disorders, with a focus on its impact on retinal ganglion cell (RGC) survival. Given that bevacizumab has been associated with adverse effects on RGCs, we aimed to validate these reports, identify an alternative VEGF inhibitor with similar antiangiogenic efficacy but without detrimental effects on RGCs, and explore the underlying mechanisms. Using primary RGCs extracted from neonatal rats and human umbilical vascular endothelial cells (HUVECs), we compared the efficacy of bevacizumab with other VEGF inhibitors and assessed the apoptotic effects and cell survival pathways influenced by these treatments. Our results showed that while both sorafenib and bevacizumab exhibited potent VEGF-inhibitory effects in HUVECs, sorafenib led to significantly higher RGC survival rates compared to bevacizumab. Western blot analysis indicated that bevacizumab treatment resulted in lower Akt levels than sorafenib, and RNA sequencing revealed that the PI3K/AKT, Ras, and MAPK signaling pathways play crucial roles in RGC viability. These findings suggest that sorafenib may offer a safer and more effective alternative to bevacizumab for treating retinal diseases, with potential implications for the development of safer therapeutic approaches, particularly in conditions like glaucoma.