Effect of Long-term Anti-VEGF Treatment on Viability and Function of RPE Cells
Anna Brinkmann1, Katrin Winkelmann1, Tom Käckenmeister1
1Department of Ophthalmology, University of Kiel, University Medical Center Kiel, Kiel, Germany.
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.
Insights
Long-term use of anti-VEGF drugs like bevacizumab and aflibercept can reduce retinal pigment epithelium (RPE) cell viability. Bevacizumab specifically may impact RPE function over extended treatment periods.
Area of Science:
- Ophthalmology
- Cell Biology
- Pharmacology
Background:
- Vascular endothelial growth factor (VEGF) antagonists are crucial in treating neovascular eye diseases.
- Long-term effects of these therapies on retinal pigment epithelium (RPE) cells remain incompletely understood.
Purpose of the Study:
- To investigate the long-term impact of clinically relevant VEGF antagonists, bevacizumab and aflibercept, on primary RPE cell function.
- To assess the effects on cell viability, TGF-ß secretion, phagocytosis, migration, RPE65 expression, and barrier function.
Main Methods:
- Primary porcine RPE cells were treated with bevacizumab or aflibercept for 1 day, 7 days, or 4 weeks.
- Assays included MTT for viability, ELISA for TGF-ß, microscopy for phagocytosis, scratch assay for migration, Western blot for RPE65, and transepithelial electrical resistance for barrier function.
Main Results:
- Both bevacizumab and aflibercept reduced RPE cell viability at all tested time points.
- TGF-ß secretion, phagocytosis, and migration were not significantly affected by either treatment.
- Bevacizumab, but not aflibercept, reduced RPE65 expression after 4 weeks; barrier function remained unaltered.
Conclusions:
- Long-term anti-VEGF therapy may compromise RPE cell viability.
- Bevacizumab treatment demonstrates potential long-term effects on RPE cell function, specifically on RPE65 expression.
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