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...

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Main Authors: Wungrak Choi, Jin-Ok Choi, Min Kyung Chae, Min Seok Kim, Chan Yun Kim
Format: Article
Language:English
Published: Nature Portfolio 2025-08-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-12199-w
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author Wungrak Choi
Jin-Ok Choi
Min Kyung Chae
Min Seok Kim
Chan Yun Kim
author_facet Wungrak Choi
Jin-Ok Choi
Min Kyung Chae
Min Seok Kim
Chan Yun Kim
author_sort Wungrak Choi
collection DOAJ
description 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.
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spelling doaj-art-626d051cd54b4186b50e00ae55f8cb5f2025-08-20T03:42:29ZengNature PortfolioScientific Reports2045-23222025-08-0115111810.1038/s41598-025-12199-wComparative analysis of bevacizumab and sorafenib on the survival of retinal ganglion cells in the treatment of retinal diseasesWungrak Choi0Jin-Ok Choi1Min Kyung Chae2Min Seok Kim3Chan Yun Kim4Department of Ophthalmology, Institute of Vision Research, Severance Hospital, Yonsei University College of MedicineDepartment of Ophthalmology, Institute of Vision Research, Severance Hospital, Yonsei University College of MedicineDepartment of Ophthalmology, Institute of Vision Research, Severance Hospital, Yonsei University College of MedicineDepartment of Ophthalmology, Institute of Vision Research, Severance Hospital, Yonsei University College of MedicineDepartment of Ophthalmology, Institute of Vision Research, Severance Hospital, Yonsei University College of MedicineAbstract 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.https://doi.org/10.1038/s41598-025-12199-wRetinal ganglion cellVascular endothelial growth factorBevacizumabSorafenibGlaucoma
spellingShingle Wungrak Choi
Jin-Ok Choi
Min Kyung Chae
Min Seok Kim
Chan Yun Kim
Comparative analysis of bevacizumab and sorafenib on the survival of retinal ganglion cells in the treatment of retinal diseases
Scientific Reports
Retinal ganglion cell
Vascular endothelial growth factor
Bevacizumab
Sorafenib
Glaucoma
title Comparative analysis of bevacizumab and sorafenib on the survival of retinal ganglion cells in the treatment of retinal diseases
title_full Comparative analysis of bevacizumab and sorafenib on the survival of retinal ganglion cells in the treatment of retinal diseases
title_fullStr Comparative analysis of bevacizumab and sorafenib on the survival of retinal ganglion cells in the treatment of retinal diseases
title_full_unstemmed Comparative analysis of bevacizumab and sorafenib on the survival of retinal ganglion cells in the treatment of retinal diseases
title_short Comparative analysis of bevacizumab and sorafenib on the survival of retinal ganglion cells in the treatment of retinal diseases
title_sort comparative analysis of bevacizumab and sorafenib on the survival of retinal ganglion cells in the treatment of retinal diseases
topic Retinal ganglion cell
Vascular endothelial growth factor
Bevacizumab
Sorafenib
Glaucoma
url https://doi.org/10.1038/s41598-025-12199-w
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