Somatostatin plays important roles in modulating neuronal functions by activating the five specific G-protein coupled receptors (sst1-sst5). Previous studies have demonstrated that sst5 were expressed in retinal ganglion cells (RGCs) and sst5 agonist attenuated the α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid-induced retinal neurotoxicity. In this study, we investigated effects and underlying mechanisms of the sst5 agonist L-817,818 on RGC injury induced by elevated intraocular pressure (COH) in experimental glaucoma. Our results showed that intraperitoneal administration of L-817,818 significantly reduced RGC loss and decreased the number of terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling (TUNEL)-positive RGCs in COH retinas, suggesting that L-817,818 may attenuate RGC apoptosis. Consistently, in COH retinas with L-817,818 administration, both the down-regulated mRNA and protein levels of anti-apoptotic Bcl-2 and the up-regulated mRNA and protein levels of pro-apoptotic Bax were partially reversed. L-817,818 administration downregulated the expression of apoptosis-related proteins caspase-9 and caspase-3 in COH retinas. In addition, L-817,818 administration reduced the concentrations of reactive oxygen species/reactive nitrogen species and malondialdehyde, and ameliorated the functions of mitochondrial respiratory chain complex (MRCC). Our results imply that administration of the sst5 agonist L-817,818 reduces RGC loss in COH rats through decreasing RGC apoptosis, which is mediated by regulating Bcl-2/Bax balance, reducing oxidative stress and rescuing activities of MRCC. Activation of sst5 may provide neuroprotective roles for RGCs in glaucoma.

生长抑素通过激活五种特定的 G 蛋白偶联受体 (sst1-sst5) 在调节神经元功能方面发挥重要作用。先前的研究表明 sst5 在视网膜神经节细胞 (RGC) 中表达，sst5 激动剂减弱了 α-氨基-3-羟基-5-甲基-4-异恶唑-丙酸诱导的视网膜神经毒性。在这项研究中，我们研究了 sst5 激动剂 L-817,818 对实验性青光眼中眼内压 (COH) 升高引起的 RGC 损伤的影响和潜在机制。我们的结果表明，L-817,818 的腹腔给药显着减少了 RGC 的损失，并减少了 COH 视网膜中末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记 (TUNEL) 阳性 RGC 的数量，表明 L-817,818 可能会减弱 RGC 细胞凋亡。一贯地，在使用 L-817,818 的 COH 视网膜中，抗凋亡 Bcl-2 的下调 mRNA 和蛋白质水平以及促凋亡 Bax 的上调 mRNA 和蛋白质水平都被部分逆转。L-817,818 给药下调 COH 视网膜中凋亡相关蛋白 caspase-9 和 caspase-3 的表达。此外，L-817,818 给药降低了活性氧/活性氮和丙二醛的浓度，并改善了线粒体呼吸链复合体 (MRCC) 的功能。我们的结果表明，sst5 激动剂 L-817,818 的给药通过减少 RGC 细胞凋亡来减少 COH 大鼠的 RGC 损失，这是通过调节 Bcl-2/Bax 平衡、减少氧化应激和挽救 MRCC 活动介导的。