Department of Ophthalmology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
Department of Ophthalmology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650034, P.R. China.
Mol Med Rep. 2018 Mar;17(3):3891-3897. doi: 10.3892/mmr.2017.8341. Epub 2017 Dec 22.
Optic nerve injury is a common disease. The present study aimed to examine the possible role of microRNA‑204 (miR‑204) in optic nerve injury through the regulation of growth‑associated protein-43 (GAP‑43). Initially, optic nerve injury models were established in Sprague‑Dawley (SD) rats, and the function of miR‑204 was either enhanced or inhibited through injection of miR‑204 mimic and inhibitor, respectively. Subsequently, the mRNA and protein levels of miR‑204, GAP‑43, toll‑like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88) and nuclear factor‑κB (NF‑κB) were examined in retinal tissues using reverse transcription‑quantitative polymerase chain reaction and western blot analyses. The apoptosis of retinal tissue cells was also detected using a terminal deoxynucleotidyl transferase mediated dUTP nick end labeling assay. There was a significant increase in the level of miR‑204 in retinal blood vessels of the model SD rats, compared with that in the normal SD rats (P<0.05), and the expression of GAP‑43 was significantly decreased (P<0.05). The results confirmed that the expression of GAP‑43 was significantly reduced, compared with that in the normal control group when the rats were treated with miR‑204 mimic (P<0.05), which was similar to the result in the model group. By contrast, its expression of GAP‑43 was significantly increased when treated with the miR‑204 inhibitor (P<0.05). Compared with the normal control group, the expression levels of TLR4, MyD88 and NF‑κB were significantly increased in the miR‑204 mimic group and model group (P<0.05), whereas the same three factors in the miR‑204 inhibitor group were effectively inhibited, compared with those in the model group, and showed similar results to the normal control group. The apoptotic rates of retinal cells in the miR‑204 mimic group and model group were significantly increased, compared with that in the normal control group (P<0.05), whereas miR‑204 inhibitor effectively reversed the effects on apoptotic rate observed in the model group, showing similar results to those in the normal control group. Taken together, miR‑204 promoted the apoptosis of retinal cells through inhibiting GAP‑43, providing theoretical guidance for the function of GAP‑43 in retinal injury.
视神经损伤是一种常见疾病。本研究旨在通过调节生长相关蛋白 43（GAP-43）来研究微小 RNA-204（miR-204）在视神经损伤中的可能作用。首先，通过注射 miR-204 模拟物和抑制剂，分别增强和抑制 Sprague-Dawley（SD）大鼠的视神经损伤模型中的 miR-204 功能。随后，使用逆转录-定量聚合酶链反应和 Western blot 分析检测视网膜组织中 miR-204、GAP-43、Toll 样受体 4（TLR4）、髓样分化因子 88（MyD88）和核因子-κB（NF-κB）的 mRNA 和蛋白水平。还使用末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记法检测视网膜组织细胞的凋亡。与正常 SD 大鼠相比，模型 SD 大鼠视网膜血管中的 miR-204 水平显着升高（P<0.05），GAP-43 的表达显着降低（P<0.05）。结果证实，当大鼠用 miR-204 模拟物处理时，与正常对照组相比，GAP-43 的表达显着降低（P<0.05），与模型组相似。相反，用 miR-204 抑制剂处理时，其 GAP-43 的表达显着增加（P<0.05）。与正常对照组相比，miR-204 模拟物组和模型组中 TLR4、MyD88 和 NF-κB 的表达水平显着升高（P<0.05），而 miR-204 抑制剂组中的这三个因素则被有效抑制，与模型组相比，结果与正常对照组相似。miR-204 模拟物组和模型组的视网膜细胞凋亡率显着升高，与正常对照组相比（P<0.05），而 miR-204 抑制剂有效逆转了模型组观察到的凋亡率的影响，与正常对照组的结果相似。综上所述，miR-204 通过抑制 GAP-43 促进视网膜细胞凋亡，为 GAP-43 在视网膜损伤中的功能提供了理论指导。
