Caspase inhibitors block the retinal ganglion cell death following optic nerve transection
Caspase inhibitors block the retinal ganglion cell death following optic nerve transection
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DOI：
10.1016/s0169-328x(99)00032-7
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发表时间：
1999-04-06
期刊：
影响因子：
--
通讯作者：
Sharma, SC
中科院分区：
文献类型：
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作者：
Chaudhary, P;Ahmed, F;Sharma, SC
视网膜节细胞在视神经切断后通过细胞凋亡而死亡。视网膜神经节细胞死亡的分子机制尚不清楚。在本研究中，我们利用RT-PCR和原位杂交技术证明了神经切断后Bcl2和BclxmRNA的表达水平下降。BAR水平在视神经切断后4天一直较高，7天后下降，10天后仍较低，CPP32水平在7天时升高，视神经切断后仍维持在较高水平。我们研究了CPP32/caspase抑制剂是否能挽救轴突切断所致的神经节细胞死亡。Caspase抑制剂DEVD-CHO(Ac-Asp-Glu-Val-Asp)和DEVD-FMK(Z-Asp-Glu-Val-Asp-FMK)在视神经切断时眼内应用，在第3天和第7天可保护约30-35%的神经节细胞免于死亡。我们进一步证明，与没有给予抑制剂的视网膜相比，给予抑制剂的视网膜中反应性小胶质细胞的数量减少。这些数据为研究视网膜神经节细胞死亡和驻留的小胶质细胞/巨噬细胞激活之间的复杂相互作用提供了新的途径。(C)1999 Elsevier Science B.V.保留所有权利。
Retinal ganglion cells die by apoptosis following axotomy. The molecular mechanisms of the retinal ganglion cell death are not well understood. In the present study using RT-PCR and in situ hybridization techniques we demonstrated that levels of mRNA for Bcl-2 and Bcl-x decreased after axotomy. Bar levels remained high until 4 days after axotomy, decreased by day 7 and remained low up to day 10. CPP32 levels increased at day 7 and remained high after optic nerve cut. We studied whether inhibitors of CPP32/caspase would save the axotomy induced ganglion cell death. DEVD-CHO (Ac-Asp-Glu-Val-aspartic acid aldehyde) and DEVD-FMK (Z-Asp-Glu-Val-Asp-FMK), caspase inhibitors, when administered intraocularly at the time of optic nerve cut, at days 3 and 7 protect about 30-35% the ganglion cells from death. We further demonstrated that the number of reactive microglia decrease in the retina when the inhibitors were given as compared with retina where no inhibitors were given. The present data offers new avenues for studying the complex interactions between the retinal ganglion cell death and the activation of resident microglia/macrophages. (C) 1999 Elsevier Science B.V. All rights reserved.