Abstract
Purpose :
The biocompatibility of intravitreal bevacizumab has been established over the past two decades for the safe and effective treatment of retinal neovascular diseases. The topical application of bevacizumab, however, for the treatment of corneal neovascularization raises concerns due to its potential corneal cytotoxicity. In this in vitro, experimental study, we evaluated the cytotoxic effects of bevacizumab on the viability and metabolism of human corneal epithelial cells (HCEpCs) and human corneal endothelial cells (HCEnCs), as well as human retinal pigment epithelial cells (ARPE-19) for comparison.
Methods :
Cell lines of HCEpCs, HCEnCs and ARPE-19 were exposed to clinically relevant concentrations of bevacizumab (0.313-5.00 mg/ml). The ApoTox-Glo Triplex Assay was used to assess cell viability, cytotoxicity and apoptosis and the Mitochondrial ToxGlo Assay was used to assess cell membrane integrity and ATP levels of the three cell types after a 24-hr. treatment period.
Results :
Across all three cell types, we observed similar results of a decrease in cell viability at 5.00 mg/ml (p<0.05) and an increase in cytotoxicity at 5.00 mg/ml (p<0.05), while apoptotic activity remained unchanged (p>0.05), which is a profile consistent with cells undergoing primary necrosis at high concentrations. Additionally, cell membrane integrity was compromised at 5.00 mg/ml (p<0.05), while no decrease in ATP levels were observed (p>0.05). This indicates no interference with mitochondrial oxidative phosphorylation in ATP production and thus, the cells were able to maintain normal metabolic levels at high concentrations.
Conclusions :
HCEpCs, HCEnCs and ARPE-19 experience a decrease in viability and undergo primary necrosis when exposed to bevacizumab at concentration of 5.00 mg/ml, however they are able to maintain normal metabolism and mitochondrial function at high concentrations used for the treatment of corneal neovascularization.
This is a 2021 ARVO Annual Meeting abstract.