Abstract
BackgroundIngrowth 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®) and bevacizumab (Avastin®) on the human corneal endothelium.MethodsHuman donor corneas, not suitable for corneal transplantation, were organ-cultured in the presence of either ranibizumab (Lucentis®) or bevacizumab (Avastin®) at different concentrations (group 1: 250 μg / ml, group 2: 25 μg / ml, group 3: 2.5 μg / 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.ResultsBackground-corrected results showed neither a significant lactate dehydrogenase (LDH) change with increasing culturing time nor a significant difference between ranibizumab (Lucentis®) and bevacizumab (Avastin®) treatment. The endothelial cell density revealed also no statistically significant difference between the two treatment groups with ranibizumab (Lucentis®) and bevacizumab (Avastin®) at all concentrations tested in this study.ConclusionsIn this study, the anti-angiogenic agents ranibizumab (Lucentis®) and bevacizumab (Avastin®) 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.
Highlights
Ingrowth of newly formed blood and lymph vessels from the limbus region into the cornea can be treated successfully by subconjunctival application of antiangiogenic agents
No statistical significant endothelial cell loss occurred during incubation with ranibizumab (Lucentis®) and bevacizumab (Avastin®) compared to the control group
Preserving of the morphology and functionality of the corneal endothelium as well as dehydration of the corneal stroma can be permanently impaired by an altered expression behavior of certain key genes
Summary
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. Single studies suggest that expression of transmembrane proteins and Na+/K+ -ATPase may occur under the Corneal avascularity and transparency are basic prerequisites for the high imaging quality of the human eye They are based essentially on the ultrastructure of the corneal stroma and a close interplay of angiogenic and antiangiogenic substances. Mechanical or chemical trauma to the cornea; this balance may be disturbed with consecutive ingrowth of blood and lymph vessels (angiogenesis) from the limbal region [8, 9]. These changes are usually associated with decreased corneal transparency and reduction of visual acuity [10].
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