Kiland Julie A, Gabelt B'ann T, Tezel Gülgün, Lütjen-Drecoll Elke, Kaufman Paul L
Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, USA.
Trans Am Ophthalmol Soc. 2009 Dec;107:146-58.
To determine the effects of the advanced glycation end product (AGE) cross-link breaker alagebrium on intraocular pressure (IOP), accommodation (ACC), outflow facility (OF), anterior segment morphology, and ocular AGE and receptors for AGE (RAGE) in older rhesus monkeys.
Six rhesus monkeys (aged 19 to 20 years) received 3 or 4 intracameral and intravitreal (final concentration, 1 mM) injections of alagebrium to one eye over 2.5 to 3 weeks and vehicle to the opposite eye. ACC and OF responses to intramuscular or intravenous pilocarpine were measured at baseline and at 1 to 2 weeks and 2, 4, and 6 months postinjection. IOP was measured prior to all injections, ACC, and OF measurements. Monkeys were euthanized 3 to 6 months after the last injection, the eyes were enucleated, and anterior and posterior segments were examined by electron microscopy or immunohistochemistry.
No significant differences were found in ACC or IOP at any time point after alagebrium treatment. Baseline OF was higher (37.0 +/- 6.0%; P < or = .005) in alagebrium-treated vs control eyes at 6 months postinjection. In 3 monkeys, alagebrium-treated eyes, compared to control eyes, showed greater focal plaque formation, similar to that seen in primary open-angle glaucoma, in the juxtacanalicular meshwork/inner wall of Schlemm's canal. No changes in anterior segment AGE or RAGE were detectable. However, some areas of the retina and optic nerve head exhibited decreased AGE and increased RAGE immunostaining.
Intraocular injection of AGE cross-link breakers is an unlikely approach for glaucoma therapy. However, it may generate a model for further study of glaucomatous-like plaque formation. Immunohistochemical changes in the posterior segment in response to alagebrium warrant further functional studies.
确定晚期糖基化终产物（AGE）交联断裂剂阿雷吉明对老年恒河猴眼压（IOP）、调节功能（ACC）、房水流出易度（OF）、眼前节形态以及眼内AGE和AGE受体（RAGE）的影响。
6只恒河猴（19至20岁）在2.5至3周内对一只眼进行3或4次前房内及玻璃体内注射阿雷吉明（最终浓度为1 mM），对侧眼注射赋形剂。在基线以及注射后1至2周、2、4和6个月时测量ACC和OF对肌肉注射或静脉注射毛果芸香碱的反应。在所有注射、ACC和OF测量之前测量IOP。在最后一次注射后3至6个月对猴子实施安乐死，摘除眼球，通过电子显微镜或免疫组织化学检查眼前节和眼后节。
阿雷吉明治疗后任何时间点的ACC或IOP均未发现显著差异。注射后6个月，阿雷吉明治疗组与对照组相比，基线OF较高（37.0 +/- 6.0%；P≤0.005）。在3只猴子中，与对照眼相比，阿雷吉明治疗的眼睛在Schlemm管邻管区小梁网/内壁出现了更大的局灶性斑块形成，类似于原发性开角型青光眼所见。未检测到眼前节AGE或RAGE的变化。然而，视网膜和视神经乳头的一些区域显示AGE免疫染色减少，RAGE免疫染色增加。
眼内注射AGE交联断裂剂不太可能成为青光眼治疗的方法。然而，它可能为进一步研究青光眼样斑块形成提供一个模型。阿雷吉明引起的眼后节免疫组织化学变化值得进一步进行功能研究。
