Treatment of ischemic retinal injury by administration of various cytokines through vitreous cavity.

通过玻璃体腔施用各种细胞因子治疗缺血性视网膜损伤。

• 批准号: 07557109
• 负责人: TAMAI Makoto
• 金额: $ 11.26万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07557109/
• 关键词: ischemia; retinal damage; cytokines; neurotrophic factors; growth factors; glutamate; excitotoxicity; liposomes

Purpose :Phosphate-activated glutaminase (PAG) activity decreases markedly in the early period of ischemia. The decrease of the enzyme activity is reversible if the ischemic period is relatively short, but it ibecomes irreversible after 90 minutes of ischemia. The deterioration is a functional damage of the retinas caused by ischemia. We studied effects of growth factors and neurotrophic factors on protection of PAG in the ischemic and reperfused rat retinas.Methods :Before ischemia, 1mul of growth factors or neurotrofic factors (0.1 mug/mul for insulin-like growth factor-l (IGF-I) , insulin-like growth factor-II (IGF-II) , brain-derived neurotrophic factor (BDNF) , nerve growth factor (NGF) ; 1 mug/mul for basic fibroblast growth factor (bFGF)) were injected into the vitreous cavity of the left eyes of anesthetized Sprague Dawley rats. As a control, phosphate buffered saline was injected to the right eyes. To induce ischemia, we clamped left eyes for 90 minutes after bulbar conjunctival incision all around limbus. The rat retinas were homogenized with distillled water 1 day after reperfusion and used for PAG assay. Retinal ammonia concentration was also determined as a ischemic marker.Results :About 80% decrease of retinal PAG activity and 50% increase of retinal ammonia concentration were observed after 90 minutes of ischemia and 1 day of reperfusion as compared with unoperated normal eyes. IGF-II,BDNF and NGF had protective effects on the retinal PAG activity, whereas IGF-I,bFGF,stable bFGF were less effective. In addition, IGF-II and BDNF suppressed elevation of retinal ammonia concentration.Conclusions :BDNF,NGF and IGF-II have marked effect on the protection of PAG activity in the ischemic and reperfused rat retinas, whereas bFGF,which is very effective for the protection of ischemic cell death, shows moderate effect.

目的：缺血早期磷酸活化转氨酶（PAG）活性明显降低。缺血时间较短时酶活性下降是可逆的，但缺血90分钟后酶活性下降不可逆。这种退化是由局部缺血引起的视网膜功能性损伤。方法：在缺血前，将1穆尔生长因子或神经营养因子（胰岛素样生长因子-I（IGF-I）、胰岛素样生长因子-II（IGF-II）、脑源性神经营养因子（BDNF）、神经生长因子（NGF）为0.1摩尔/穆尔;碱性成纤维细胞生长因子（bFGF）为1摩尔/穆尔）注射到麻醉的Sprague道利大鼠左眼的玻璃体腔中。作为对照，将磷酸盐缓冲盐水注射到右眼。为了诱导缺血，我们在利姆布斯周围的球结膜切口后夹住左眼90分钟。再灌注后1天，用蒸馏水将大鼠视网膜匀浆并用于PAG测定。结果：缺血90 min再灌注1d后，视网膜PAG活性下降约80%，视网膜氨浓度升高约50%。IGF-II、BDNF和NGF对视网膜PAG活性有保护作用，而IGF-I、bFGF和稳定性bFGF的保护作用较弱。结论：BDNF、NGF和IGF-II对缺血再灌注大鼠视网膜PAG活性有明显的保护作用，而bFGF对缺血再灌注大鼠视网膜PAG活性的保护作用较弱。

项目成果

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