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Matthew McDonald, Michael Wormstone, Julie Ann Eldred; Vascular Endothelial Growth Factor Plays A Key Role In Posterior Capsule Opacification after Cataract Surgery. Invest. Ophthalmol. Vis. Sci. 2016;57(12):2021. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Half of global blindness is caused by cataract, which is the most commonly performed surgical procedure worldwide. Posterior Capsule Opacification (PCO), a fibrotic wound healing response post-cataract surgery, develops in up to half of patients, causing secondary vision loss. In the current study, we assess the putative role of VEGF in this response and the therapeutic benefit of targeting this molecule.
The human lens epithelial cell line FHL124 which has a 99.5% similarity in gene expression to native lens epithelium was employed. Features of PCO including cell viability, cell death, epithelial to mesenchymal transition (EMT), and matrix contraction were evaluated against both VEGF application and pan-VEGF receptor inhibition by Axitinib. Due to the ubiquitous role TGFβ is reported to play in PCO and fibrosis, experiments were also performed in the presence and absence of this molecule. WST-1 assay was used to evaluate cell viability and the LDH assay for cell death assessment. Matrix contraction was determined by the patch contraction assay. EMT was examined using QRT PCR and western blot to detect the myofibroblast marker alpha smooth muscle actin (α-SMA).
Addition of 100ng/ml VEGF alone did not stimulate any significant change in the output measures assessed. 10ng/ml TGFβ promoted EMT and matrix contraction. Treatment of TGFβ stimulated cells with VEGF did not significantly affect this response. However, treatment with 10µM Axitinib caused a reduction in cell viability which was associated with increased cell death. VEGF inhibition also decreased α-SMA levels relative to baseline at the gene and protein level. Moreover, the marked increase in EMT observed with TGFβ was attenuated by Axitinib. TGFβ induced contraction was also suppressed when VEGF was inhibited.
Lens epithelial cells produce an endogenous supply of VEGF that plays an important role in cell survival, growth, EMT, and matrix contraction that contributes to PCO after cataract surgery. Strategies to target VEGF/VEGFR signalling could provide a valuable therapeutic approach for the prevention and management of PCO.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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