Wang Xue, Yuan Zhi-Lan
Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, 211166, China.
Department of Ophthalmology, The First People's Hospital of Lianyungang, Lianyungang, 222000, China.
Int Ophthalmol. 2019 Oct;39(10):2303-2312. doi: 10.1007/s10792-018-01071-8. Epub 2019 Jan 12.
The objective of this work was to find out the effects of nuclear factor erythroid 2-related factor/heme oxygenase-1 (Nrf2/HO-1) pathway on retinal ganglion cell (RGC) injury in glaucoma.
The chronic ocular hypertension (COH) rat models of glaucoma were constructed, and intraocular pressure (IOP) and RGC numbers were detected at different time points. Additionally, rats were divided into normal group (normal control rats), model group (COH model rats), and model + tBHQ group (COH model rats treated with Nrf activator, tBHQ). RGC apoptosis was detected by using TUNEL staining, and the expressions of Nrf2/HO-1 were detected by qRT-PCR and western blotting.
COH model rats showed significant IOP elevation and the increased mRNA and protein expressions of Nrf2 and HO-1 from 1 to 6 weeks after operation, with the evidently decreased RGC numbers at 4 weeks and 6 weeks after operation (all P < 0.05). Besides, rats in the model group had increased apoptosis index (AI) of RGCs and the elevated mRNA and protein expressions of Nrf2/HO-1 with remarkably reduced RGC numbers when compared with normal control rats, but the model rats treated with tBHQ exhibited an apparent decrease in AI of RGCs, as well as remarkable increases in RGC numbers and the mRNA and protein expression of Nrf2/HO-1 (all P < 0.05).
Activation of Nrf2/HO-1 pathway significantly reduced the apoptosis and injury of RGCs in rats with chronic ocular hypertension (COH), thereby protecting RGCs in glaucoma, which could be a promising clinical target to prevent RGC degeneration in glaucoma.
本研究旨在探究核因子红细胞2相关因子/血红素加氧酶-1（Nrf2/HO-1）通路对青光眼视网膜神经节细胞（RGC）损伤的影响。
构建慢性高眼压（COH）大鼠青光眼模型，于不同时间点检测眼压（IOP）及RGC数量。此外，将大鼠分为正常组（正常对照大鼠）、模型组（COH模型大鼠）和模型+tBHQ组（用Nrf激活剂tBHQ处理的COH模型大鼠）。采用TUNEL染色检测RGC凋亡，通过qRT-PCR和蛋白质印迹法检测Nrf2/HO-1的表达。
COH模型大鼠术后1至6周眼压显著升高，Nrf2和HO-1的mRNA及蛋白表达增加，术后4周和6周RGC数量明显减少（均P<0.05）。此外，与正常对照大鼠相比，模型组大鼠RGC凋亡指数（AI）增加，Nrf2/HO-1的mRNA及蛋白表达升高，RGC数量显著减少，但用tBHQ处理的模型大鼠RGC的AI明显降低，RGC数量以及Nrf2/HO-1的mRNA和蛋白表达显著增加（均P<0.05）。
激活Nrf2/HO-1通路可显著减少慢性高眼压（COH）大鼠RGC的凋亡和损伤，从而保护青光眼患者的RGC，这可能是预防青光眼RGC变性的一个有前景的临床靶点。
