Ahmed F A, Hegazy K, Chaudhary P, Sharma S C
Department of Ophthalmology, New York Medical College, Valhalla, NY 10595, USA.
Brain Res. 2001 Sep 21;913(2):133-9. doi: 10.1016/s0006-8993(01)02759-7.
Brimonidine, a selective alpha(2)-adrenoceptor agonist, has recently been shown to be neuroprotective as it significantly improves survival of retinal ganglion cells (RGCs) after calibrated optic nerve injury in rats. In the present study, we examined the effect of brimonidine (alpha(2)-adrenoceptor agonist) on RGC survival after increased intraocular pressure (IOP) in adult rats. RGCs were prelabeled by bilateral tectal injection of 5% Fluoro-Gold (FG). Two days later, unilaterally IOP was increased 2.2-2.5 times (28-30.5 mmHg) that of the normal pressure (12.5-14.5 mmHg) by cauterization of three episcleral veins. The elevated IOP was maintained throughout the duration of the experiment. Rats were treated intraperitoneally with brimonidine (1 mg/kg) or phosphate-buffered saline (PBS) once per week beginning either before (group A) or after (group B) increasing the IOP. Another group of rats was left as the control with elevated IOP but without any brimonidine/PBS treatment. Rats were euthanized at 3, 4 and 5 weeks after IOP elevation. Identifiable RGCs were counted and compared between control and experimental groups. Brimonidine significantly protected RGCs from elevated IOP-induced cell death. In control rats with three-vein cauterization, there was 5-6% cell death per week. Almost all RGCs were protected following brimonidine treatment for 3 weeks both in groups A and B. At 4 weeks, there was 4.5% cell death in group A and 6.5% in group B. At 5 weeks, cell death was 5.9% in group A and 6.2% in group B. The difference in cell death in groups A and B was insignificant. No significant differences were observed between PBS-treated and control groups. No significant changes in elevated IOP was found after brimonidine or PBS treatment when compared with the nontreated control group. Although pressure remained elevated throughout the length of the experiment, 3 weeks later the amount of cell death gradually increased in brimonidine-treated animals.
溴莫尼定是一种选择性α₂肾上腺素能受体激动剂，最近的研究表明它具有神经保护作用，因为在大鼠经校准的视神经损伤后，它能显著提高视网膜神经节细胞（RGCs）的存活率。在本研究中，我们检测了溴莫尼定（α₂肾上腺素能受体激动剂）对成年大鼠眼压升高后RGCs存活的影响。通过双侧顶盖注射5%荧光金（FG）对RGCs进行预标记。两天后，通过烧灼三条巩膜静脉，使单侧眼压升高至正常眼压（12.5 - 14.5 mmHg）的2.2 - 2.5倍（28 - 30.5 mmHg）。在整个实验过程中，眼压一直维持在升高状态。从眼压升高前（A组）或眼压升高后（B组）开始，大鼠每周腹腔注射一次溴莫尼定（1 mg/kg）或磷酸盐缓冲盐水（PBS）。另一组大鼠作为眼压升高但未接受任何溴莫尼定/PBS治疗的对照组。在眼压升高后3、4和5周对大鼠实施安乐死。对对照组和实验组中可识别的RGCs进行计数并比较。溴莫尼定能显著保护RGCs免受眼压升高诱导的细胞死亡。在接受三条静脉烧灼的对照大鼠中，每周有5 - 6%的细胞死亡。在A组和B组中，经溴莫尼定治疗3周后，几乎所有的RGCs都得到了保护。在4周时，A组细胞死亡率为4.5%，B组为6.5%。在5周时，A组细胞死亡率为5.9%，B组为6.2%。A组和B组细胞死亡的差异不显著。PBS治疗组和对照组之间未观察到显著差异。与未治疗的对照组相比，溴莫尼定或PBS治疗后眼压升高无显著变化。尽管在整个实验过程中眼压一直维持在升高状态，但3周后，溴莫尼定治疗的动物中细胞死亡数量逐渐增加。
