Inhibition of preretinal proliferation by free radical scavengers in an experimental model of tractional retinal detachment

Abstract

An original model of experimental proliferative vitreoretinopathy consisting of an intravitreal injection of 10 7 human platelets and 1 IU of hyaluronidase was developed in pigmented rabbits. One group of 11 eyes served as non-treated controls. Two other groups of 11 eyes each received Ginkgo Biloba extracts which are known free radical scavengers (EGb761, Ipsen, France), given orally in two doses, 50 mg kg -1 day -1 and 100 mg kg -1 day -1 respectively, from the day after the platelet injection to the end of the first month. The fourth group (11 eyes) was intravenously injected with a unique dose of 15000 U kg -1 of superoxide dismutase the day after platelet injection. All animals were ophthalmoscopically examined in a masked fashion twice a week for 1 month and killed at the end of the experiment for histological analysis. Vitreoretinal proliferation was graded according to a six-stage classification. The non-treated eyes showed a high rate of retinal detachment (11/11 eyes), with a mean final score of 3·91 ± 0·94. Histologic examinations consistently showed retinal retraction by fibrocellular preretinal membranes spreading to both surfaces of the retina as well as preretinal neovascularization. Many cells positively reacted with anti-cytokeratin or anti-vimentin monoclonal antibodies. All three groups of treated eyes showed significantly lower scores of vitreoretinal proliferation at almost each time point of examination. At the end of the study, five retinal detachments were found in the EGb761 group at 50 mg kg -1 day 1 (mean final score 2·45 ± 1·37), only one in the group receiving 100 mg kg -1 day -1 (mean score 1·64 ± 1·03), and one in the SOD treated eyes. The lowest mean score found at day 28 was observed in the group receiving SOD (1·36 ± 1·43), although this group presented during the first 3 weeks with an intense vitreous and sometimes anterior chamber inflammation. Statistical comparison between treatments did not show significant differences at most time points of the study. These results demonstrate that antioxidants may efficiently prevent preretinal proliferation, in clinicopathological entities where free radicals had not yet been shown to play a direct pathogenetic role. They are also among the first attempts for inhibiting preretinal proliferations with non-cytotoxic agents and using a non-ocular route.