急性高眼压模型中p75NTR抑制剂对视网膜神经节细胞作用的研究

doi:10.3969/j.issn.1006-7795.2017.01.005

首都医科大学学报 ›› 2017, Vol. 38 ›› Issue (1): 24-28.doi: 10.3969/j.issn.1006-7795.2017.01.005

急性高眼压模型中p75^NTR抑制剂对视网膜神经节细胞作用的研究

汪晓磊¹, 马建民², 孟照洋¹, 尹奕¹, 王艳玲¹

1. 首都医科大学附属北京友谊医院眼科, 北京 100050;
2. 首都医科大学附属北京同仁医院眼科, 北京 100730

收稿日期:2016-11-28 出版日期:2017-01-21 发布日期:2017-01-20
通讯作者: 汪晓磊 E-mail:wang1xiaolei@126.com
基金资助:
首都医科大学基础-临床科研合作基金（14JL32），首都医科大学重点实验室开放研究课题（2015YKSJ02）。

Roles of p75^NTR inhibitor on retinal ganglion cells in a rat model of acute ocular hypertension

Wang Xiaolei¹, Ma Jianmin², Meng Zhaoyang¹, Yin Yi¹, Wang Yanling¹

1. Department of Ophthalmology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China;
2. Department of Ophthalmology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China

Received:2016-11-28 Online:2017-01-21 Published:2017-01-20
Supported by:
This study was supported by Clinical-Basic Cooperation Program from Capital Medical University(14JL32),Beijing Ophthalmology and Visual Sciences Key Laboratory (2015YKSJ02).

摘要/Abstract

摘要： 目的验证通过抑制p75^NTR（p75 neurotrophin receptor）可降低急性高眼压（acute ocular hypertension，AOH）对视网膜神经节细胞（retinal ganglion cells，RGCs）的损伤作用。方法应用大鼠急性高眼压模型，玻璃体腔注射p75^NTR抑制剂（TAT-Pep5），按建模后1、3、5 d取材，分为正常对照组、假手术组、急性高眼压组、急性高眼压+TAT-Pep5组。采用免疫荧光技术、Western blotting等方法检测急性高眼压模型中相关蛋白的表达变化。TdT介导的dUTP缺口末端标记（TUNEL）染色检测细胞凋亡情况。结果急性高眼压模型视网膜Müller细胞上proNGF表达增加。注射p75^NTR抑制剂TAT-Pep5后急性高眼压视网膜上cleaved-caspase 3蛋白量减少，并且RGCs凋亡数目减少。结论视网膜神经节细胞损伤可引起proNGF表达增加，选择性阻断Müller细胞上的p75^NTR或干预其信号传导通路，可以减少急性高眼压模型中RGCs凋亡。

关键词: 急性高眼压, p75^NTR, 神经生长因子前体, TAT-Pep 5抑制剂, Mü, ller细胞

Abstract: Objective To explore the role of p75^NTR inhibitor on suppressing retinal ganglion cells (RGCs) apoptosis in a rat model of acute ocular hypertension. Methods The acute ocular hypertension (AOH) rat model was established, and animals were divided into control (Ctrl), sham operation, AOH, AOH+TAT-Pep5 treated groups (1,3 and 5d subgroups). Immunofluorescent staining was performed to detect the expression of proNGF and p75^NTR. Western blotting was used to detect the protein expression levels of proNGF and cleaved-caspase 3. TUNEL assay was used to detect cell apoptosis. Results The expression of proNGF was increased in acute ocular hypertension model. When the p75^NTR was blocked by its inhibitor (TAT-Pep5), the number of death RGCs (TUNEL positive cell number) were less than that of AOH group. The results of Western blotting showed that the protein expression levels of cleaved-caspase 3 could be up-regulated in retina from AOH group or down-regulated in retina from AOH+TAT-Pep5 group when compared with that of Ctrl and AOH groups. Conclusion RGCs injury can increase proNGF expression. p75^NTR blockade can potentiate the survival of RGCs.

Key words: acute ocular hypertension, p75^NTR, proNGF, TAT-Pep 5 inhibitor, Müller cell

中图分类号:

R775

汪晓磊, 马建民, 孟照洋, 尹奕, 王艳玲. 急性高眼压模型中p75^NTR抑制剂对视网膜神经节细胞作用的研究[J]. 首都医科大学学报, 2017, 38(1): 24-28.

Wang Xiaolei, Ma Jianmin, Meng Zhaoyang, Yin Yi, Wang Yanling. Roles of p75^NTR inhibitor on retinal ganglion cells in a rat model of acute ocular hypertension[J]. Journal of Capital Medical University, 2017, 38(1): 24-28.

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急性高眼压模型中p75^NTR抑制剂对视网膜神经节细胞作用的研究

Roles of p75^NTR inhibitor on retinal ganglion cells in a rat model of acute ocular hypertension

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急性高眼压模型中p75NTR抑制剂对视网膜神经节细胞作用的研究

Roles of p75NTR inhibitor on retinal ganglion cells in a rat model of acute ocular hypertension

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急性高眼压模型中p75^NTR抑制剂对视网膜神经节细胞作用的研究

Roles of p75^NTR inhibitor on retinal ganglion cells in a rat model of acute ocular hypertension