Abstract
Purpose: :
To investigate the effects of Bevacizumab (Avastin®) on Human Microvascular Endothelial Cells (HMEC-1) in vitro and to explore the potential toxic effect of suprachoroidal injection of Bevacizumab on the posterior segment of the rat eye.
Methods: :
Subconfluent HMEC-1 were treated with 0,003, 0,03 and 0,3 mg/mL of Bevacizumab. Cell viability was evaluated at 24 h using MTT assays. For in vivo experiments, we used 8 weeks old Lewis rats. One month after Bevacizumab (20µl, 10mg/ml) supra choroidal injection, semi-thin and tomato lectin staining were performed to examine Bevacizumab induced changes of the choroidal vasculature. Control eye were injected with saline (20µl).
Results: :
Bevacizumab at all tested doses did not induce any significant reduction of HMEC-1 viability. Semi-thin sections of the retina did not demonstrate a significant reduction of retinal thickness and particularly no reduction of the outer nuclear layer thickness. The vascular tomato lectin staining analysis revealed that Bevacizumab mostly affected the choroidal vasculature with an increased avascular area in the choriocapillaries.
Conclusions: :
Bevacizumab does not appear to be toxic to human microvascular endothelial cells. In vivo, even when injected in the supra choroidal space, close to the outer retina, no toxic effect was observed on retinal morphology. However, a significant reduction of vascular area could be observed in the choriocapillaries suggesting that long-term exposure may reduce the choiocapillaries circulation. Clinical consequences of such an effect should be carefully analyzed.
Keywords: drug toxicity/drug effects • choroid • cell survival