Survival and axonal regeneration of off-center retinal ganglion cells of adult cats are promoted with an anti-glaucoma drug, nipradilol, but not BDNF and CNTF

Survival and axonal regeneration of off-center retinal ganglion cells of adult cats are promoted with an anti-glaucoma drug, nipradilol, but not BDNF and CNTF
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DOI:
10.1016/j.neuroscience.2007.05.042
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发表时间:
2007-08
期刊:
影响因子:
3.3
通讯作者:
T. Yata;M. Nakamura;H. Sagawa;Y. Tokita;H. Terasaki;M. Watanabe
T. Yata;M. Nakamura;H. Sagawa;Y. Tokita;H. Terasaki;M. Watanabe
中科院分区:
医学3区
文献类型:
--
作者:
T. Yata;M. Nakamura;H. Sagawa;Y. Tokita;H. Terasaki;M. Watanabe

文献摘要

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当视网膜神经节细胞再生轴突进入移植的周围神经时,偏离中心的视网膜神经节细胞(RGC)比ON的RGC占据更小的比例。我们研究了当用脑源性神经营养因子(BDNF)+睫状神经营养因子(CNTF)+毛喉素(BCF)或抗青光眼药物3,4-二氢-8-(2-羟基-3-异丙基氨基)-丙氧基-3-硝基氧基-2H-1-苯并吡喃(nipradilol)增加再生RGCs的数量时,是否促进了成年猫OFF RGCs的再生能力。ON或OFF RGCs的形态学确定的基础上,他们的树枝状分支在内部网状层使用计算分析。在正常完整视网膜中,ON和OFF RGC的比率(ON/OFF比率)为1.25(55%/44%),而在周围神经移植后6周注射生理盐水的再生RGC(对照)中,ON/OFF比率为2.61。再生ON和OFF RGC的估计数量分别为2149和895。注射BCF仅增加ON RGC的数量至5766(对照的2.7倍),但不增加OFF RGC的数量,n=858。尼普拉洛增加了ON(11,518,对照的5.4倍)和OFF RGC(7330,对照的8.2倍)的估计数量。在视神经(OpN)切断和玻璃体内注射生理盐水,BCF-或nipradilol的视网膜中,存活的ON和OFF RGC的数量显示出与再生RGC相似的趋势。因此,尼普拉地洛促进ON和OFF RGCs的存活和再生能力,而BCF仅促进ON RGCs的能力。原肌球蛋白相关激酶B(BDNF受体)在内丛状层外2/3处分布较稀疏。OFF-RGC的存活能力较低可能部分归因于其分布。
OFF-center retinal ganglion cells (RGCs) occupy a smaller proportion than ON RGCs when RGCs regenerate axons into a transplanted peripheral nerve. We examined whether the regeneration ability of OFF RGCs in adult cats was promoted when the numbers of regenerating RGCs were increased with brain-derived neurotrophic factor (BDNF)+ciliary neurotrophic factor (CNTF)+forskolin (BCF) or 3,4-dihydro-8-(2-hydroxy-3-isopropylamino)-propoxy-3-nitroxy-2H-1-benzopyran (nipradilol), an anti-glaucoma drug. ON or OFF RGCs were morphologically determined on the basis of their dendritic ramification in the inner plexiform layer using computational analysis. In the normal intact retina the ratio of ON and OFF RGCs (ON/OFF ratio) was 1.25 (55%/44%); whereas, it was 2.61 in regenerating RGCs with saline injection (control) 6 weeks after peripheral nerve transplantation. Estimated numbers of regenerating ON and OFF RGCs were 2149 and 895, respectively. An injection of BCF increased only numbers of ON RGCs into 5766 (2.7-fold to control) but not that of OFF RGCs, n=858. Nipradilol increased both estimated numbers of ON (11,518, 5.4-fold to control) and OFF RGCs (7330, 8.2-fold to control). In the retinas with optic nerve (OpN) transection and intravitreal saline-, BCF- or nipradilol-injection, numbers of ON and OFF RGCs surviving axotomy showed similar trend to that in regenerating RGCs. Thus, nipradilol promoted the survival and regeneration abilities of both of ON and OFF RGCs whereas BCF only did the abilities of ON RGCs. The distribution of tropo-myosin-related kinase B, BDNF receptor, was sparser in the outer two thirds of inner plexiform layer. The lower surviving ability of OFF-RGCs may be attributed in part to the distribution.