Department of Ophthalmology, Affiliated Hospital of Southwest Medical University, Luzhou, China.
Department of Pathology, Affiliated Hospital of Southwest Medical University, Luzhou, China.
Acta Biochim Biophys Sin (Shanghai). 2019 Apr 1;51(4):411-421. doi: 10.1093/abbs/gmz020.
To investigate the neuroprotective effects of the mitochondria-targeted antioxidant Szeto-Schiller peptide 31 (SS-31) in a rat experimental glaucoma model, SS-31 was intraperitoneally (IP) injected into Sprague-Dawley rats, followed by intracameral injection of polystyrene microspheres to induce elevated intraocular pressure (IOP). After 6 weeks, electroretinography (ERG) and flash visual-evoked potentials (F-VEPs) were recorded to assess retinal function. Hematoxylin-eosin staining was performed on retinal cross-sections to measure ganglion cell complex (GCC) thickness. Apoptotic retinal cells were assessed by TUNEL staining. Brn3a-positive retinal ganglion cells (RGCs) were counted in retinal flat mounts via immunofluorescence. The retinal total SOD, SOD2, and MDA expression levels were assessed in retinal tissue homogenates. The cyt c, Bax, and Bcl-2 protein levels in rat retinas were detected by western blot analysis. Bax and Bcl-2 expressions were also evaluated using immunohistochemistry in paraffinized sections. Our results showed that the rats that received microsphere injection developed elevated IOP. SS-31 ameliorated the reductions in the a- and b-wave amplitudes on ERG and the F-VEP amplitude in glaucomatous eyes. GCC thickness was preserved, TUNEL-positive cells were decreased in the retina, and Brn3a-positive RGCs were increased in the SS-31-treated glaucoma group compared with those in the non-treated glaucoma group. SS-31 significantly reduced MDA levels and increased SOD2 levels after glaucoma induction. Significant suppression of cyt c release, upregulation of Bcl-2, and downregulation of Bax were observed following SS-31 administration. In summary, SS-31 exerts neuroprotective effects in this experimental glaucoma model by inhibiting mitochondrial dysfunction and therefore represents a promising therapeutic agent for glaucoma.
为了研究线粒体靶向抗氧化剂 Szeto-Schiller 肽 31（SS-31）在大鼠实验性青光眼模型中的神经保护作用，将 SS-31 腹腔内（IP）注射到 Sprague-Dawley 大鼠中，然后在眼内注射聚苯乙烯微球以诱导眼内压升高（IOP）。6 周后，记录视网膜电图（ERG）和闪光视觉诱发电位（F-VEP）以评估视网膜功能。进行视网膜横截面苏木精-伊红染色以测量节细胞复合体（GCC）厚度。通过 TUNEL 染色评估凋亡的视网膜细胞。通过免疫荧光在视网膜平面铺片中计数 Brn3a 阳性视网膜神经节细胞（RGCs）。在视网膜组织匀浆中评估视网膜总 SOD、SOD2 和 MDA 表达水平。通过 Western blot 分析检测大鼠视网膜中细胞色素 c、Bax 和 Bcl-2 蛋白水平。还通过免疫组化在石蜡切片中评估 Bax 和 Bcl-2 的表达。我们的结果表明，接受微球注射的大鼠出现了升高的 IOP。SS-31 改善了青光眼眼中 ERG 的 a 波和 b 波幅度以及 F-VEP 幅度的降低。与未经治疗的青光眼组相比，SS-31 治疗的青光眼组中 GCC 厚度得以保留，视网膜中 TUNEL 阳性细胞减少，Brn3a 阳性 RGCs 增加。SS-31 在诱导青光眼后显著降低 MDA 水平并增加 SOD2 水平。SS-31 给药后观察到细胞色素 c 释放明显抑制、Bcl-2 上调和 Bax 下调。总之，SS-31 通过抑制线粒体功能障碍在该实验性青光眼模型中发挥神经保护作用，因此代表了一种有前途的青光眼治疗药物。
