Protection of the rat retina from ischemic injury by brain-derived neurotrophic factor, ciliary neurotrophic factor, and basic fibroblast growth factor.
Protection of the rat retina from ischemic injury by brain-derived neurotrophic factor, ciliary neurotrophic factor, and basic fibroblast growth factor.
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发表时间：
1994-03
影响因子：
4.4
通讯作者：
Kazuhiko Unoki;M. Lavail
中科院分区：
文献类型：
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作者：
Kazuhiko Unoki;M. Lavail
目的观察三种促存活剂对大鼠视网膜缺血损伤的保护作用。这些药物包括脑源性神经营养因子（BDNF）、睫状神经营养因子（CNTF）和碱性成纤维细胞生长因子（bFGF）。方法将刘易斯白化病大鼠眼内压升高至160 mm Hg，持续90 min，造成视网膜缺血。在缺血损伤之前或之后的不同时间玻璃体内注射试剂或缓冲液对照，并且缺血后存活时间为7或14天。通过细胞学分析、测量几层的厚度和神经节细胞层的神经元计数从塑料包埋切片评估视网膜损伤的程度。结果视网膜缺血时视网膜内层变薄，细胞数量减少，但感光细胞核层无明显变化。每种药物在缺血前2天注射时都能短暂改善退行性变化。在缺血后7天，视网膜内层的损害要少得多，更多的神经节细胞比缓冲液注射或未注射的眼睛。在缺血后14天，保护作用不再明显，除了在BDNF治疗的眼睛的内核层。如果在缺血损伤后5天进行第二次BDNF注射，则在缺血后14天，视网膜内层比缓冲液对照组保存得更好，但神经节细胞的存活没有增强。在缺血后1天或3天单次注射BDNF，与注射缓冲液的对照组相比，降低了视网膜内层损伤的程度，并增加了存活神经节细胞的数量。(CNTF和bFGF没有用缺血后注射进行研究。结论BDNF、CNTF和bFGF在缺血前2d对压力诱导的视网膜缺血性损伤具有短暂的保护作用，缺血后再次注射BDNF可延长其保护作用。此外，即使在缺血损伤后仅1或3天应用BDNF时，也可以看到BDNF提供的保护，尽管缺血后1天的保护作用大于3天。
PURPOSE The protective effects of three survival-promoting agents on ischemia-induced retinal injury in the rat were investigated. The agents included brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), and basic fibroblast growth factor (bFGF). METHODS Retinal ischemia was induced in Lewis albino rats by increasing intraocular pressure to 160 mm Hg for 90 minutes. The agents or buffer controls were injected intravitreally at different times, either before or after the ischemic insult, and the postischemic survival time was either 7 or 14 days. The degree of retinal damage was assessed from plastic-embedded sections by cytologic analysis, measurement of the thickness of several layers, and neuronal counts of the ganglion cell layer. RESULTS Retinal ischemia thinned and reduced cell numbers in the inner retinal layers, but not in the photoreceptor nuclear layer. Each agent transiently ameliorated the degenerative changes when it was injected 2 days before ischemia. At 7 days postischemia, the inner retinal layers were far less damaged, and more ganglion cells were present than in buffer-injected or uninjected eyes. The protective effect was no longer evident at 14 days postischemia, except in the inner nuclear layer of the BDNF-treated eyes. If a second injection of BDNF was made 5 days after the ischemic insult, then the inner retinal layers were more preserved than buffer controls at 14 days postischemia, but the survival of ganglion cells was not enhanced. A single injection of BDNF at either 1 or 3 days postischemia reduced the degree of inner retinal damage and increased the number of surviving ganglion cells over that in buffer-injected controls. (CNTF and bFGF were not studied with postischemic injections.) CONCLUSIONS BDNF, CNTF, and bFGF transiently protect the retina from pressure-induced ischemic injury when given 2 days before ischemia, and a second injection of BDNF given postischemically can prolong the protective effect. Moreover, protection afforded by BDNF can be seen even when applied only 1 or 3 days after the ischemic insult, although the protective effect is greater at 1 day than at 3 days postischemia.