EFFECT OF RESVERATROL AND BEVACIZUMAB ON EXPERIMENTAL CORNEAL NEOVASCULARIZATION Selim Doganay, MD¹; Penpe Gul Firat, MD¹; Cem Cankaya, MD¹; Hale Kirimlioglu, MD 2 Inonu University School of Medicine, Malatya-Turkey ¹ Department of Ophthalmology, ² Department of Pathology, Authors have no financial or proprietary interest in any instrument or products used in this study

Purpose  To evaluate effects of resveratrol and bevacizumab on experimental corneal neovascularization. EFFECT OF RESVERATROL AND BEVACIZUMAB ON EXPERIMENTAL CORNEAL NEOVASCULARIZATION

Introduction  It has been shown that vascular endothelial growth factor (VEGF) stimulates corneal neovascularization in animal models. 1-4  Bevacizumab is a recombinant humanized murine monoclonal antibody that binds, and inhibits the biological activity of all human VEGF-A isoforms. 5-7  Resveratrol is an agent which directly inhibits the tumor growing in an unknown mechanism. It has been shown that resveratrol has anti-angiogenic properties. 8,9

Materials and methods  Corneal alkali burn was performed by touching central cornea with a standard 7 mm diameter 1 N NaOH-soaked Whatman 3 filter paper for 2 minutes in 62 eyes of 31 male white Vienna rabbits.  We waited seven days for the effect of chemical cauterization to be appear. The rabbits were then divided randomly into four groups. EFFECT OF RESVERATROL AND BEVACIZUMAB ON EXPERIMENTAL CORNEAL NEOVASCULARIZATION

(n: Number of eyes, DMS: Dimetil sulfoksid, NaCl: Sodium clor solution n drug Group 116 Resveratrol ( 10 mg/ml ml, solved in DMS solution) Group 216 DMS (0.05 ml) Group 316 Bevacizumab ( 10 mg/ ml 0.05 ml, diluated in % 0.9 NaCl) Group 414 NaCl (0.05 ml % 0.9) Drugs were administered to the both eyes of rabits by subconjunctival injection for 7 days EFFECT OF RESVERATROL AND BEVACIZUMAB ON EXPERIMENTAL CORNEAL NEOVASCULARIZATION

 Corneal photos were taken by Nikon FS-3 biomicroscopy 15 days after alkali injury.  Inflamatuar index (ciliary injection, central corneal edema, peripheral corneal edema) was analyzed as previously described. 10  Corneal neovascularization areas were calculated as unit square on photograps with Auto CAD program in all groups. EFFECT OF RESVERATROL AND BEVACIZUMAB ON EXPERIMENTAL CORNEAL NEOVASCULARIZATION

Results  According to inflamatuar index scores, there was no significant difference among the group 1-2 and group 2-4 (p< Bonferoni Mann- Whitney U test)  There was a significant difference according to the inflamatuar index scores among the group 2-3 and group 3-4. EFFECT OF RESVERATROL AND BEVACIZUMAB ON EXPERIMENTAL CORNEAL NEOVASCULARIZATION

 A significant difference was obtained between the group 1 and group 3 for the central and peripheral corneal edema scores.  The calculation of corneal neovascularization area in group 3 was significantly smaller than the other groups. EFFECT OF RESVERATROL AND BEVACIZUMAB ON EXPERIMENTAL CORNEAL NEOVASCULARIZATION

Bevacizumab DMSO NACL Resveratrol EFFECT OF RESVERATROL AND BEVACIZUMAB ON EXPERIMENTAL CORNEAL NEOVASCULARIZATION

Groups New Vascularization area (Unit square) EFFECT OF RESVERATROL AND BEVACIZUMAB ON EXPERIMENTAL CORNEAL NEOVASCULARIZATION

Conclusions  Subconjunctival administration of bevacizumab inhibits corneal neovascularization effectively in the rabbit corneal alkali burn model.  No effect of resveratrol to the corneal neovascularization on experimental model of corneal alkali burn was seen at the doses of usage. EFFECT OF RESVERATROL AND BEVACIZUMAB ON EXPERIMENTAL CORNEAL NEOVASCULARIZATION

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