Investigating the effect of de-escalating dose of bevacizumab on vascular endothelial growth factor-A gene expression of Retinal pigmented epithelium
Mohammadreza Mojarad1 *, M. Hossein Nowroozzadeh1 , Mohammad Reza Khalili1 , Fatemeh Sanie-Jahromi1
- Poostchi Ophthalmology Research Center, Department of Ophthalmology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
Abstract: Retinopathy of prematurity (ROP) remains a major cause of childhood vision loss globally. Despite advances in neonatal care, the rising incidence of ROP necessitates continual exploration of therapeutic strategies. Anti-vascular endothelial growth factor (VEGF) therapy has emerged as a promising treatment, yet concerns persist about its transient efficacy, potential adverse effects on angiogenesis, and systemic implications.
Methods: This study investigates the impact of de-escalating doses of bevacizumab (x to x/64; x = 312.5 µg) on VEGF-A and angiotensinogen (AGT) gene expression in retinal pigmented epithelium (RPE) cells. RPE cells were cultured and exposed to hypoxic conditions, mimicking ROP scenarios. Various concentrations of bevacizumab were administered, and gene expression was analyzed using real-time PCR.
Results: The hypoxic RPE exhibited approximately a 0.5-fold change in AGT expression and a 1.5-fold change in VEGF expression compared to the control RPE. Lower concentrations of bevacizumab (? x/8) induced a significant increase in AGT expression in hypoxic condition. VEGF expression showed no significant changes at higher concentrations but markedly increased at the lowest studied dose (x/64).
Conclusion: This study highlights the divergent effects of different de-escalating doses of bevacizumab on VEGF and AGT gene expression at the mRNA level. Bevacizumab concentrations as low as 1/64 of the standard dose led to a secondary increase in VEGF, which could potentially challenge its clinical efficacy in the context of hypoxic retina. The increase in AGT expression was observed at concentrations ≤ 1/8x, the implications of which should be investigated through proper in vivo or clinical studies.
