The effects of an anti-vegf agent bevacizumab in an ischemia-reperfusion model of retina

OBJECTIVE: To create a model of ischemic retina by temporary ischemia and reperfusion and examine the possible anti-apoptotic and neurodegenerative effects of a VEGF antagonist.MATERIALS AND METHODS: In this study, 18 Wistar, albino, 4 - 6 months, approximately 200-300 g. weighing rats were used. After deep anesthesia retinal ischemia was induced by raising intraocular pressure which stopped blood flow to the eye by retinal arteries. Intraocular pressure was increased by connectting a bottle of sterile saline to the anterior chamber through cornea. Intraocular pressure was measured by portable (Tono-Pen). Target intraocular pressure was 90 mmhg. This pressure was continued for 45 minutes and then reperfusion was allowed. For the first group ischemia was induced but an anti-VEGF agent was not given. For the second group two days before ischemia 0.05 ml (1.25mg)of the most commonly used intravitreal anti-VEGF agent, bevacizumab, was administered intravitrealy and then ischemic model was created. The last group?s intraocular pressure was not increased as being the control group , only a cannula was introduced into the anterior chamber through the cornea. In the in study only one eye of each rat was used because the injection made to one eye was likely to affect the other eye by the systemic route as mentioned in the literature. Intravitreal injection was performed by a 30 gauge needle under sterile conditions into the mid-vitreous cavity from the superotemporal quadrant 2mm posterior to the limbus. Before injection pupil was dilatated by 2.5% tropicamide and phenylephrine hydrochloride 0.5%. For topical anesthesia HCL propakain was used and sterilization was achieved by dropping 5% povidone-iodine on the conjunctiva.After euthanasia 6 animals from each group were subjected to histomorphometric and four were subjected to immunohistochemical and histopathologic examinations. For histomorphometric examination the number of retinal ganglion cells was counted by optical dissector method. For immunohistochemistry, VEGF levels and apoptosis were examined in the retinal tissue.RESULTS: It was observed that in ischemia reperfusion injury bevacizumab reduces retinal ganglion cell death and apoptosis. It was also identified that although a large molecule bevacizumab effec ts the choroid and reduces the amount of VEGF in this tissue.DISCUSSION: Even though VEGF is a neurotrophic molecule, in the ischemia-reperfusion injury bevacizumab treatment which is an anti-VEGF agent decreases apoptosis