Abstract
Purpose :
Anti-vascular endothelial growth factors (VEGF) have been used as an adjuvant in eyes undergoing pars-plana vitrectomy. However, the precise effect is unknown and concerns remain regarding its profibrotic activity. So, we aimed to evaluate angiogenic and fibrotic gene expression on fibrovascular membranes of eyes undergoing pars-plana vitrectomy for complications of proliferative diabetic retinopathy.
Methods :
we analyzed fibrovascular membranes (FVMs) from 10 eyes: 4 eyes pretreated with intravitreal bevacizumab and six control eyes. FVMs were digested into single cells, separated into endothelial cells vs non-endothelial cell fractions (supernatant), mRNA was extracted from each fraction separately, and the transcriptome was measured by RT-qPCR. We then compared the relative expression of genes involved in angiogenesis and endothelial cell integrity including VEGFA and its receptors (FLT1 and KDR), angiopoietins (ANGPT1 and ANGPT2), vascular endothelial cadherin (CDH5), and endothelin (EDN1) and its receptors. Additionally genes involved in fibrosis formation such as TGFβ, CTGF, and TAGLN, and myofibroblast products including FN1, VIM and αSMA were also evaluated.
Results :
Bevacizumab resulted in significant reduction of endothelial expression of VEGFA, VEGF receptors (FLT1 and KDR), and angiopoietin 2 (ANGPT2) as well as an increased expression CDH5 and EDN1, suggesting reduced angiogenesis and enhanced vascular integrity. A strong correlatin was observed among ANGPT2 gene expression and VEGFA and its receptors. Immunohistochemical staining showed increased nuclear translocation of FOXO1 after IVB, which could be the underlying mechanism for increased expression of EDN1 (figure 1). The non-endothelial cell fraction showed decreased expression of VEGFA and fibronectin (FN1), without significant changes in the expression of profibrotic factors.
Conclusions :
Our findings indicate that adjuvant preoperative anti-VEGF effectively counteracts factors related to abnormal vascular status by modifying VEGFA signaling pathway in endothelial cells (figure 2). Profibrotic genes profile remained relatively unaltered.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.