Baudouin C, Ettaiche M, Imbert F, Droy-Lefaix M T, Gastaud P, Lapalus P
Department of Ophthalmology, Saint-Roch Hospital, Nice, France.
Exp Eye Res. 1994 Dec;59(6):697-706. doi: 10.1006/exer.1994.1155.
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.
在有色家兔中建立了一种实验性增殖性玻璃体视网膜病变的原始模型，该模型通过玻璃体内注射10(7)个人血小板和1 IU透明质酸酶构建。一组11只眼睛作为未治疗的对照。另外两组各11只眼睛分别接受银杏叶提取物（已知的自由基清除剂，法国益普生公司的EGb761），从血小板注射后的第二天开始，以50 mg kg-1天-1和100 mg kg-1天-1两种剂量口服，持续至第一个月末。第四组（11只眼睛）在血小板注射后的第二天静脉注射单次剂量15000 U kg-1的超氧化物歧化酶。所有动物每周两次以盲法进行眼底镜检查，持续1个月，并在实验结束时处死进行组织学分析。玻璃体视网膜增殖根据六阶段分类法进行分级。未治疗的眼睛显示出高比例的视网膜脱离（11/11只眼睛），最终平均评分为3.91±0.94。组织学检查一致显示视网膜因纤维细胞性视网膜前膜向视网膜两面蔓延以及视网膜前新生血管形成而发生回缩。许多细胞与抗细胞角蛋白或抗波形蛋白单克隆抗体呈阳性反应。所有三组治疗的眼睛在几乎每个检查时间点的玻璃体视网膜增殖评分均显著较低。在研究结束时，50 mg kg-1天-1的EGb761组发现5例视网膜脱离（平均最终评分为2.45±1.37），接受100 mg kg-1天-1的组仅1例（平均评分为1.64±1.03），超氧化物歧化酶治疗的眼睛中有1例。在第28天观察到接受超氧化物歧化酶治疗的组平均评分最低（1.36±1.43），尽管该组在最初3周出现强烈的玻璃体炎症，有时还有前房炎症。在研究的大多数时间点，各治疗组之间的统计学比较未显示出显著差异。这些结果表明，在尚未证明自由基起直接致病作用的临床病理实体中，抗氧化剂可能有效预防视网膜前增殖。它们也是首次尝试用非细胞毒性药物并通过非眼部途径抑制视网膜前增殖。
