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The Effects of Anti-vascular Endothelial Growth Factor Agents on Human Retinal Pigment Epithelial Cells Under High Glucose Conditions

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Specialty Ophthalmology
Date 2017 Mar 3
PMID 28251077
Citations 4
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Abstract

Aim: To investigate the effects of high glucose levels and anti-vascular endothelial growth factor (VEGF) agents (bevacizumab, ranibizumab and aflibercept) on retinal pigment epithelium (RPE) cells.

Methods: ARPE-19 cells were cultured at different glucose levels (5.5 mmol/L, 25 mmol/L, and 75 mmol/L). Cell viability was evaluated by MTT assay at 3d after treatment with D-glucose. Cell migration ability was measured by wound healing assay at 3d. A cell death detection kit was used to assess apoptosis at 3 and 14d. Cell proliferation was assessed by EdU assay at 3d. The culture medium was treated with anti-VEGF agents at clinically relevant concentrations. The experiment was then repeated at a different glucose level.

Results: The viability and migration of ARPE-19 cells were significantly decreased in the presence of 75 mmol/L as compared to 5.5 mmol/L glucose. The percentage of TUNEL-positive cells was significantly increased and the proliferative potential was decreased with 75 mmol/L compared to 5.5 mmol/L glucose. There were no significant differences in the results between 25 mmol/L and 5.5 mmol/L glucose. In the presence of 75 mmol/L glucose, the groups treated with anti-VEGF showed decreased cell viability and proliferation and increased apoptosis. However, there were no significant differences between the anti-VEGF groups.

Conclusion: High glucose level decreases the viability, wound healing ability, and proliferation of RPE cells, while increasing apoptosis. Furthermore, anti-VEGF agents interfered with the physiological functions of RPE cells under high-glucose conditions, accompanied by decreases in cell viability and proliferation.

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References
1.
Schnichels S, Hagemann U, Januschowski K, Hofmann J, Bartz-Schmidt K, Szurman P . Comparative toxicity and proliferation testing of aflibercept, bevacizumab and ranibizumab on different ocular cells. Br J Ophthalmol. 2013; 97(7):917-23. DOI: 10.1136/bjophthalmol-2013-303130. View

2.
Miura Y, Klettner A, Roider J . VEGF antagonists decrease barrier function of retinal pigment epithelium in vitro: possible participation of intracellular glutathione. Invest Ophthalmol Vis Sci. 2010; 51(9):4848-55. DOI: 10.1167/iovs.09-4699. View

3.
Treumer F, Klettner A, Baltz J, Hussain A, Miura Y, Brinkmann R . Vectorial release of matrix metalloproteinases (MMPs) from porcine RPE-choroid explants following selective retina therapy (SRT): towards slowing the macular ageing process. Exp Eye Res. 2012; 97(1):63-72. DOI: 10.1016/j.exer.2012.02.011. View

4.
Klettner A, Mohle F, Roider J . Intracellular bevacizumab reduces phagocytotic uptake in RPE cells. Graefes Arch Clin Exp Ophthalmol. 2010; 248(6):819-24. DOI: 10.1007/s00417-010-1317-x. View

5.
Klettner A, Tahmaz N, Dithmer M, Richert E, Roider J . Effects of aflibercept on primary RPE cells: toxicity, wound healing, uptake and phagocytosis. Br J Ophthalmol. 2014; 98(10):1448-52. DOI: 10.1136/bjophthalmol-2014-305105. View