Unoki K, LaVail M M
Department of Ophthalmology, University of California, San Francisco 94143-0730.
Invest Ophthalmol Vis Sci. 1994 Mar;35(3):907-15.
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).
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.
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.)
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.
研究三种促生存因子对大鼠缺血性视网膜损伤的保护作用。这些因子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）。
通过将Lewis白化大鼠的眼压升高至160 mmHg持续90分钟诱导视网膜缺血。在缺血损伤之前或之后的不同时间将这些因子或缓冲液对照玻璃体内注射，缺血后存活时间为7天或14天。通过细胞学分析、测量几层的厚度以及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程度。
视网膜缺血使视网膜内层变薄并减少细胞数量，但光感受器核层未受影响。当在缺血前2天注射时，每种因子都能短暂改善退行性变化。在缺血后7天，视网膜内层的损伤远小于注射缓冲液或未注射的眼睛，并且存在更多的神经节细胞。除了BDNF处理的眼睛的内核层外，缺血后14天保护作用不再明显。如果在缺血损伤后5天进行第二次BDNF注射，那么在缺血后14天视网膜内层比缓冲液对照保存得更好，但神经节细胞的存活未得到增强。在缺血后1天或3天单次注射BDNF可减轻视网膜内层损伤程度，并增加存活神经节细胞的数量，超过注射缓冲液的对照组。（未研究缺血后注射CNTF和bFGF的情况。）
BDNF、CNTF和bFGF在缺血前2天给予时可短暂保护视网膜免受压力诱导的缺血性损伤，缺血后第二次注射BDNF可延长保护作用。此外，即使在缺血损伤后仅1天或3天应用BDNF也能看到保护作用，尽管缺血后1天的保护作用比3天更大。
