Effect of Long-term Anti-VEGF Treatment on Viability and Function of RPE Cells

ABSTRACT

Purpose/Aim of the study

Vascular endothelial growth factor (VEGF)-antagonists are given over long time periods in the clinic, but the long-term effects on retinal pigment epithelium (RPE) cells are not fully investigated. This study aims to investigate these effects with two clinical relevant VEGF antagonists, bevacizumab and aflibercept, on the function of primary RPE cells.

Materials and Methods

All tests were conducted with primary porcine RPE. Cells were stimulated with bevacizumab or aflibercept (both 250 µg/ml) for 1 day, 7 days or 4 weeks. Cell viability was tested in MTT Assay. Secretion of TGF-ß was tested in ELISA, phagocytosis in a microscopic assay, migration in a scratch assay, and expression of RPE65 in Western blot. Barrier function was tested for bevacizumab in transwell-cultured cells by measuring transepithelial electrical resistance for up to 3 days.

Results

Viability was reduced by both antagonists at all time points tested. TGF-ß secretion was not altered by any treatment. Phagocytosis was not significantly reduced by any treatment. Wound healing ability was not significantly altered by any treatment. The expression of RPE65 was reduced by bevacizumab but not aflibercept after 4 weeks. Transepithelial electrical resistance was not altered.

Conclusions

Long-term treatment with anti VEGF may affect viability of RPE cells, and treatment with bevacizumab may have effects on RPE function in long-term treatment.

KEYWORDS:

• Bevacizumab
• aflibercept
• retinal pigment epithelium (RPE)
• phagocytosis
• RPE65
• TGF-ß

Declaration of interest

The authors have no conflict of interest.

Additional information

Funding

This work was supported by the Dr Jackstädt Foundation under Grant 19/07/2016. AK has been partly supported by the Stifterverband under Grant H17057015020215353.