Abstract
Purpose::
To study the effects of subconjunctival injection of bevacizumab (Avastin®) on angiogenesis and metalloproteinases activity in the cornea of rats submitted to silver nitrate injury
Methods::
Male Wistar rats, aging 8 to 10 weeks, were used. Under general anesthesia silver nitrate was used to perform chemical cauterization of the cornea. The animals were divided in four groups: control group (CG) that received a subconjunctival injection of 0,02 ml of 0,9% saline solution; group GO that received 0,02 ml of bevacizumab just after the lesion; group G3 that received bevacizumab at day 3 after lesion and G5 that received bevacizumab at day 5 after lesion. All animals were euthanized at day 7 after lesion. The new formed vessels were quantified after China Ink perfusion and photographs were obtained and analyzed in a computadorized system (Image Pro-Plus®). The activity of metalloproteinases MMP-2 and MMP-9 were evaluated by zimography in a pool of corneas obtained from animals submitted to the same model and treatment schedule.
Results::
In the control group, neovascularization covered 53.56% ± 15.11 (mean ± SD) of the corneal surface, compared with 35.57%±18.80 (mean ± SD) in the G0 group, 30.60% ± 11.82 (mean ± SD) in the G3 and 35.86% ± 0.07 (mean ± SD) in the G5. Zymography showed a slight reduction in matrix metalloproteinases activity when bevacizumab was administrated at the moment of injury and a most significant reduction at day 3. At day 5 zymography showed an increase of the activity of these metalloproteinases
Conclusions::
The results showed an inhibition of angiogesenis when the control group were compared with all treated groups. There were no statistic differences when vascular density was compared between treated groups. These results may indicate that bevacizumab was able to inhibit corneal angiogenesis and that there was no influence of the injection day. Together these results may indicate that the subconjunctival injection of bevacizumab may have a therapeutic potential as an antiangiogenic agent and that matrix metalloproteinases activity decreased, but not at significant levels, demanding more investigations regarding to the interaction of bevacizumab and activity of matrix metalloproteinases.
Keywords: cornea: basic science • neovascularization • extracellular matrix