Our study assesses the effects of anti-VEGF (Vascular Endothelial Growth Factor) drugs and Trichostatin A (TSA), an inhibitor of histone deacetylase (HDAC) activity, on cultured ARPE-19 (Adult Retinal Pigment Epithelial-19) cells that are immortalized human retinal pigment epithelial cells. ARPE-19 cells were treated with the following anti-VEGF drugs: aflibercept, ranibizumab, or bevacizumab at 1× and 2× concentrations of the clinical intravitreal dose (12.5 μL/mL and 25 μL/mL, respectively) and analyzed for transcription profiles of genes associated with the pathogenesis age-related macular degeneration (AMD). HDAC activity was measured using the Fluorometric Histone Deacetylase assay. TSA downregulated and genes, and upregulated and genes. TSA alone or bevacizumab plus TSA showed a significant reduction of HDAC activity compared to untreated ARPE-19 cells. Bevacizumab alone did not significantly alter HDAC activity, but increased gene expression of and and caused downregulation of and . Combination of bevacizumab plus TSA increased gene expression of and , and reduced and . In conclusion, we demonstrated that anti-VEGF drugs can: (1) alter expression of genes involved in oxidative stress ( and ), inflammation ( and ) and apoptosis ( and ), and (2) TSA-induced deacetylation altered transcription for angiogenesis (), apoptosis, and inflammation genes.
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| http://dx.doi.org/10.3390/cells10040878 | DOI Listing |
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