Bevacizumab De-Escalating Doses and VEGF-A/AGT Gene Expression
Description
This study explores the cellular mechanisms of low-dose anti-VEGF therapy for retinopathy of prematurity (ROP) and its severe form, plus disease. The research specifically examines the expression of VEGF-A and angiotensinogen (AGT) genes in retinal pigment epithelium (RPE) cells under hypoxic conditions, mimicking ROP. RPE cells were treated with varying doses of bevacizumab (312.5 µg/mL to 4.9 µg/mL), and gene expression was analyzed. Hypoxia decreased AGT expression by 0.5-fold and increased VEGF-A expression by 1.5-fold. Interestingly, bevacizumab doses below 39.1 µg/mL significantly upregulated AGT, while the lowest dose (4.9 µg/mL) unexpectedly increased VEGF-A. Bioinformatics analysis highlighted VEGFA as a central hub in the direct interaction network, while AGT exhibited notable bottleneck properties within the broader hypoxia‑associated network. The findings suggest that bevacizumab concentrations between 19.5 and 9.8 μg/mL are optimal for ROP treatment. This range stabilizes VEGF-A expression while potentially reducing plus disease by increasing AGT expression, underscoring the critical need for precise dose optimization in ROP therapy.