Effects of ranibizumab on human corneal endothelial cells

Background Ingrowth of newly formed blood and lymph vessels (angiogenesis) from the limbus region into the cornea can be treated successfully by subconjunctival application of antiangiogenic agents. Currently, there are several angiogenesis inhibitors from various manufacturers available, such as vascular endothelial growth factor (VEGF) antibodies. The aim of the study was to investigate potential cytotoxic effects of two anti-VEGF agents, ranibizumab (Lucentis[R]) and bevacizumab (Avastin[R]) on the human corneal endothelium. Methods Human donor corneas, not suitable for corneal transplantation, were organ-cultured in the presence of either ranibizumab (Lucentis[R]) or bevacizumab (Avastin[R]) at different concentrations (group 1: 250 [mu]g / ml, group 2: 25 [mu]g / ml, group 3: 2.5 [mu]g / ml) for a period of up to 4 weeks. Microscopic imaging for endothelial cell counting, detection of morphologic alterations of the endothelium, and molecular biology testing (Enzyme-linked Immunosorbent Assay [ELISA]) for metabolic changes was performed. Results Background-corrected results showed neither a significant lactate dehydrogenase (LDH) change with increasing culturing time nor a significant difference between ranibizumab (Lucentis[R]) and bevacizumab (Avastin[R]) treatment. The endothelial cell density revealed also no statistically significant difference between the two treatment groups with ranibizumab (Lucentis[R]) and bevacizumab (Avastin[R]) at all concentrations tested in this study. Conclusions In this study, the anti-angiogenic agents ranibizumab (Lucentis[R]) and bevacizumab (Avastin[R]) demonstrated no cytotoxic effects on the corneal endothelium of human organ-cultured donor corneas over the limited study time period of 4 weeks. However, based on the study design (in-vitro) and the limited follow-up period, no conclusions on potential long-term effects can be drawn. Keywords: Corneal neovascularization, Corneal endothelial cells, Corneal angiogenesis, Vascular endothelial growth factor, Ranibizumab, Bevacizumab