Department of Biochemistry, Akdeniz University Medical School, Campus, 07070 Antalya, Turkey.
Exp Eye Res. 2011 Oct;93(4):387-96. doi: 10.1016/j.exer.2011.05.008. Epub 2011 Jun 12.
This study aimed to clarify the possible therapeutic benefit of preferential nitric oxide synthase (NOS) inhibition and catalytic antioxidant Mn (III) meso-tetrakis (N-n-hexylpyridinium-2-yl) porphyrin (MnTnHex-2-PyP(5+)) treatment in a rat model of elevated intraocular pressure (EIOP). Rats were randomly divided into different experimental groups which received either intraperitoneal MnTnHex-2-PyP(5+) (0.1 mg/kg/day), intragastric NOS inhibitor (S-methylthiourea: SMT; 5 mg/kg/day) or both agents for a period of 6 weeks. Ocular hypertension was induced by unilaterally cauterizing three episcleral vessels and the unoperated eye served as control. Neuroprotective effects of given treatments were determined via electrophysiological measurements of visual evoked potentials (VEP) while retina and vitreous levels of MnTnHex-2-PyP(5+) were measured via LC-MS/MS. Latencies of all VEP components (P(1), N(1), P(2), N(2), P(3)) were significantly prolonged (p < 0.05) in EIOP and returned to control levels following all three treatment protocols. Ocular hypertension significantly increased retinal protein nitration (p < 0.001) which returned to baseline levels in all treated groups. NOS-2 expression and nitrate/nitrite levels were significantly greater in non-treated rats with EIOP. Retinal TUNEL staining showed apoptosis in all ocular hypertensive rats. The presented data confirm the role of oxidative injury in EIOP and highlight the protective effect of MnTnHex-2-PyP(5+) treatment and NOS inhibition in ocular hypertension.
本研究旨在阐明优先抑制一氧化氮合酶（NOS）和催化抗氧化剂 Mn（III）meso-四（N-正己基吡啶-2-基）卟啉（MnTnHex-2-PyP（5+））治疗在高眼压（EIOP）大鼠模型中的可能治疗益处。大鼠被随机分为不同的实验组，分别接受腹腔内 MnTnHex-2-PyP（5+）（0.1mg/kg/天）、胃内 NOS 抑制剂（S-甲基硫脲：SMT；5mg/kg/天）或两种药物治疗 6 周。通过单侧烧灼三个巩膜血管来诱导眼内高压，未手术眼作为对照。通过视觉诱发电位（VEP）的电生理测量来确定给予治疗的神经保护作用，同时通过 LC-MS/MS 测量视网膜和玻璃体内的 MnTnHex-2-PyP（5+）水平。所有 VEP 成分（P1、N1、P2、N2、P3）的潜伏期在 EIOP 中均显著延长（p<0.05），并在所有三种治疗方案后均恢复到对照水平。眼内高压显著增加视网膜蛋白硝化（p<0.001），所有治疗组均恢复到基线水平。NOS-2 表达和硝酸盐/亚硝酸盐水平在未治疗的 EIOP 大鼠中显著增加。视网膜 TUNEL 染色显示所有高眼压大鼠均有凋亡。所提供的数据证实了氧化损伤在 EIOP 中的作用，并强调了 MnTnHex-2-PyP（5+）治疗和 NOS 抑制在眼内高压中的保护作用。
