Bevacizumab does not affect autophagy clearance during proteasomal inhibition in human retinal pigment epithelial cells

The most common reason for blindness in developed countries is age-related macular degeneration (AMD) that can be classified into two main categories: the atrophic, or dry form and the exudative, or wet form. The diagnostic difference between dry and wet AMD is the development of choroidal neovascularization in wet AMD. A master regulator in the development of neovascularization is Vascular Endothelial Growth Factor (VEGF) A, which is therapeutically inhibited to treat wet AMD. Current VEGF-antagonists are the FabFragment ranibizumab (Lucentis), the fusion protein aflibercept (Eylea) and the off-label used antibody bevacizumab (Avastin). Due to its low costs, Avastin is largely used worldwide in clinics. Recent findings reveal that proteasomal and lysosomal clearance systems including autophagy have been disturbed in AMD. Failure of autophagy in aged postmitotic cells, including retinal pigment epithelial (RPE) cells, can result in accumulation of aggregate-prone proteins, cellular degeneration and finally, cell death that secondarily lead to photoreceptor damage and visual loss. In this study, we show that bevacizumab does not affect autophagy clearance in ARPE-19 cell during proteasome inhibition and protein aggregation.