Effects of minocycline and tetracycline on retinal ganglion cell survival after axotomy
Effects of minocycline and tetracycline on retinal ganglion cell survival after axotomy
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DOI：
10.1016/j.neuroscience.2005.04.011
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发表时间：
2005-01-01
期刊：
影响因子：
3.3
通讯作者：
Kelly, MEM
中科院分区：
文献类型：
--
作者：
Baptiste, DC;Powell, KJ;Kelly, MEM
在本研究中，我们比较了腹腔注射四环素和米诺环素在成年大鼠视神经单侧轴突切除术后增强视网膜神经节细胞（RGC）存活率的体内神经保护功效。我们还检查了四环素药物对视网膜小胶质细胞激活的影响。通过荧光金逆行标记使视网膜整体中的 RGC 可视化。使用 OX-42 单克隆抗体通过免疫组织化学方法证实了活化小胶质细胞的存在。视神经轴切术导致 RGC 死亡并增加小胶质细胞的激活。 5 天前未观察到明显的 RGC 损失，第 7 天和 14 天分别发生约 50% 和 80-90% 的细胞损失。检查四环素和米诺环素对轴突切除后 7 天的 RGC 存活的影响，发现与仅用载体（对照的 52%）和四环素治疗的动物（对照的 58%）相比，米诺环素治疗的动物（非轴突切除对照的 75%）的 RGC 数量增加。对照、载体、四环素和米诺环素处理的轴切动物的 RGC 密度 (RGC(s)/mm(2) +/- S.D.) 分别为 1996 81、1029 186、1158 190 和 1497 312。在 7 天时观察到的米诺环素的神经保护作用是短暂的，因为在轴突切除后 14 天，米诺环素治疗的动物中存在的 RGC（281 +/- 43，对照的 14%）与媒介物治疗的动物（225 +/- 47，对照的 11%）没有显着差异。与仅接受载体的轴突动物相比，四环素和米诺环素治疗的轴突动物中活化的视网膜小胶质细胞的OX-42染色减少。这些结果表明，全身施用第二代四环素衍生物米诺环素可通过可能与抑制小胶质细胞活化有关的机制延迟轴突型 RGC 的死亡。视神经轴突切除术后米诺环素的神经保护功效优于四环素。 (c) 2005 年由 Elsevier Ltd 代表 IBRO 出版。
In the present study, we compared the in vivo neuroprotective efficacy of intraperitoneally administered tetracycline and minocycline to enhance the survival of retinal ganglion cells (RGCs) following unilateral axotomy of the adult rat optic nerve. We also examined the effects of the tetracycline drugs on the activation of retinal microglia. RGCs in retinal whole-mounts were visualized by retrograde labeling with fluorogold. The presence of activated microglia was confirmed immunohistochernically using OX-42 monoclonal antibodies. Optic nerve axotomy produced RGC death and increased activation of microglia. No significant RGC loss was seen prior to 5 days and approximately 50% and 80-90% cell loss occurred at 7 and 14 days, respectively. Examination of the effects of tetracycline and minocycline on RGC survival at 7 days post-axotomy, revealed increased numbers of RGCs in minocycline-treated animals (75% of non-axotomized control) compared with vehicle-only (52% of control) and tetracycline-treated (58% of control) animals. The densities of RGCs (RGC(s)/mm(2) +/- S.D.) for control, vehicle-, tetracycline- and minocycline-treated axotomized animals were 1996 81, 1029 186, 1158 190 and 1497 312, respectively. The neuroprotective effect of minocycline seen at 7 days was transient, since RGCs present in minocycline-treated animals at 14 days post-axotomy (281 +/- 43, 14% of control) were not significantly different to vehicle-treated animals (225 +/- 47, 11% of control). OX-42 staining of activated retinal microglia was reduced in tetracycline- and minocycline-treated axotomized animals compared with axotomized animals receiving vehicle-only. These results demonstrate that systemic administration of the second-generation tetracycline derivative, minocycline, delays the death of axotomized RGCs by a mechanism that may be associated with inhibition of microglia activation. The neuroprotective efficacy of minocycline following optic nerve axotomy was superior to that of tetracycline. (c) 2005 Published by Elsevier Ltd on behalf of IBRO.