Vascular endothelial growth factor plays a key role in posterior capsule opacification after cataract surgery

Session Details

Session Title: Posterior Capsule Opacification

Session Date/Time: Sunday 11/09/2016 | 08:30-10:00

Paper Time: 08:36

Venue: Hall C2

First Author: : M.McDonald UK

Co Author(s): :    M. Wormstone   J. Eldred                 

Abstract Details

Purpose:

Half of global blindness is caused by cataract, which is the most commonly performed surgical procedure worldwide. Posterior Capsule Opacification (PCO), the wound healing response post-cataract surgery, develops in up to half of patients, causing secondary vision loss. Vascular endothelial growth factor (VEGF) signalling may play a key role in this process, which means licensed VEGF-targeted therapy applied during cataract surgery could improve the quality of life for millions.

Setting:

School of Biological Sciences, University of East Anglia, Norwich, NR4 7TJ, UK

Methods:

Lens epithelial cell line FHL 124 and an in-vitro capsular bag culture model isolated from human donor eyes was employed. Constituents of PCO including cell viability, death, epithelial to mesenchymal transition (EMT), and matrix contraction were tested against both VEGF application and pan-VEGF receptor inhibition. WST-1 cell viability assay, LDH death assay, immunocytochemistry, matrix contraction assay, QRT PCR, western blot, and phase contrast microscopy in human tissue models were employed to test this hypothesis.

Results:

Addition of 100ng/ml VEGF alone did not stimulate any significant change in the output measures assessed. However, VEGFR inhibition inhibited all parameters of PCO significantly. Cell viability was decreased, cell death increased, contraction did not occur in matrix contraction assays, and genes coding for fibrotic markers and matrix components were also downregulated (α-SMA, Fibronectin 1, SNAIL1/2, Collagen I, MMP-2). A significant decrease in rates of PCO was also observed in the capsular bag model relative to control.

Conclusions:

Lens epithelial cell’s endogenous supply of VEGF is key for survival, proliferation, migration, and matrix contraction in the wound healing response post-cataract surgery. Inhibition of VEGFRs leads to a dramatic reduction in markers of fibrosis and matrix regulatory genes, and consequently PCO.

Financial Disclosure:

NONE