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

目的：磷酸活化谷氨酰胺酶（PAG）活性在缺血早期明显降低。如果缺血时间较短，酶活性的降低是可逆的，但缺血90分钟后，酶活性的降低就不可逆了。这种退化是由缺血引起的视网膜功能损伤。我们研究了生长因子和神经营养因子对缺血和再灌注大鼠视网膜PAG的保护作用。方法：缺血前用生长因子或神经生长因子1ml(胰岛素样生长因子- 1 （IGF-I）、胰岛素样生长因子- 2 （IGF-II）、脑源性神经营养因子（BDNF）、神经生长因子（NGF） 0.1 mg / ml；将1杯/瓶碱性成纤维细胞生长因子（bFGF）注入麻醉大鼠左眼玻璃体腔内。作为对照，向右眼注射磷酸盐缓冲盐水。为了诱导缺血，我们在球结膜边缘周围切口后夹持左眼90分钟。大鼠视网膜再灌注1天后用蒸馏水匀浆，用于PAG测定。测定视网膜氨浓度作为缺血标志物。结果：缺血90 min再灌注1 d后，视网膜PAG活性较未手术正常眼降低80%，视网膜氨浓度升高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bFGF的保护作用较弱。此外，IGF-II和BDNF抑制视网膜氨浓度升高。结论：BDNF、NGF和IGF-II对缺血和再灌注大鼠视网膜PAG活性的保护作用显著，而bFGF对缺血细胞死亡的保护作用非常有效，但作用一般。

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.