Effects of EGb761 and superoxide dismutase in an experimental model of retinopathy generated by intravitreal production of superoxide anion radical

Background: A study was carried out to investigate the effect of two antiox idants - Ginkgo biloba extract (EGb761) and superoxide dismutase (SOD)- in an experimental model of vitreoretinopathy obtained by direct production of oxygen free radicals in the vitreous cavity. Methods: Twenty-eight pigment ed rabbits were used. Vitreoretinopathy was induced by intravitreal injecti on of 50 mu l of a mixture composed of 40 nmol of xanthine and 0.001 IU of xanthine oxidase. Rabbits were randomly distributed into four groups: Group 1 (n=8) did not receive any treatment and served as a positive control. Gr oups 2 (n=8) and 3 (n=8) received for 1 month EGb761 given orally at a dose of 100 mg/kg/day, respectively 1 day after and 1 week before induction of retinopathy. Group 4 (n=4) was treated by three intramuscular injections of 15 000 IU/kg of SOD, 24 h before induction and 24 and 48 h thereafter. Cli nical evaluations and electroretinograms (ERG) were repeatedly performed un til the animals were killed at day 28. Histological examinations and immuno histological procedures were performed to ascertain the origin and characte ristics of the cellular proliferation and to compare vitreoretinal structur es in the four groups. Results: Intravitreal injection of xanthine-xanthine oxidase produced a strong inflammatory response with vitreous infiltrates and epiretinal membrane formation, inconstantly associated with retinal det achment. ERG showed a decrease of the a-, b- and c-waves beginning within a few hours after injection. Histologic evaluation found an intravitreal and epiretinal infiltration by leukocytes and epithelial-derived cells, dense vitreoretinal membranes and retinal detachments with occasional neovascular ization. In the treated groups (groups 2-4), all clinical, electric and his tologic data were significantly improved compared to the control group. How ever, no difference could be found among the three treated groups. Conclusi on: This study demonstrates the strong pathologic effects of free radical p roduction on the retina and the close relationships between free radicals, inflammatory pathways and vitreoretinal proliferative disorders. It also co nfirms the pharmacological interest of prevention by antioxidants and free radical scavengers.