Efficacy and safety of memantine treatment for reduction of changes associated with experimental glaucoma in monkey, II: Structural measures
Efficacy and safety of memantine treatment for reduction of changes associated with experimental glaucoma in monkey, II: Structural measures
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DOI：
10.1167/iovs.03-0567
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发表时间：
2004-08-01
影响因子：
4.4
通讯作者：
Wheeler, L
中科院分区：
文献类型：
--
作者：
Hare, WA;WoldeMussie, E;Wheeler, L
目的。为了通过解剖学测量，确定每日口服美金刚是否安全有效，以减少与实验性青光眼相关的损伤。方法：用Ar激光前房角治疗18只猕猴右眼诱发慢性高眼压(COHT)。9只动物每天口服美金刚4 mg/kg，其余9只只给予赋形剂。定期测量所有动物双眼的眼压(IOP)。在整个研究过程中，通过在多个时间点获得的立体眼底照片记录了视神经头、视网膜血管和周围视网膜的外观。视神经头部地形图的测量是从眼压升高后大约3个月、5个月和10个月眼压最高的动物身上进行的共聚焦激光扫描获得的。在眼压升高后大约16个月，处死动物，进行视网膜神经节细胞层(RGC)细胞的组织学计数。结果：组织学测量显示，对于中度眼压升高的动物，美金刚治疗与提高下视网膜RGC的存活有关。视神经头部地形图的测量显示，美金刚治疗的动物眼压引起的变化较少。这一效应在对视杯和神经视网膜边缘的测量中都能看到。在两个治疗组的正常血压眼中，这些相同的组织学和形态学测量的比较表明，美金刚治疗对这些眼睛没有任何显著影响。结论：RGC存活率的组织学测量和脑部地形图的断层测量表明，美金刚(一种不降低眼压的化合物)全身治疗在减少与实验性青光眼相关的变化方面是安全有效的。
PURPOSE. To determine, using anatomic measurements, whether daily oral dosing with memantine is both safe and effective to reduce the injury associated with experimental glaucoma in primates.METHODS. Argon laser treatment of the anterior chamber angle was used to induce chronic ocular hypertension (COHT) in the right eyes of 18 macaque monkeys. Nine animals were daily orally dosed with 4 mg/kg memantine while the other nine animals received vehicle only. Measurements of intraocular pressure (IOP) from both eyes of all animals were made at regular intervals. Appearance of the optic nerve head, retinal vessels, and surrounding retina was documented with stereo fundus photographs obtained at multiple time points throughout the study. Measurements of optic nerve head topography were obtained from confocal laser scans made from animals with the highest IOPs at approximately 3, 5, and 10 months after elevation of IOP. At approximately 16 months after IOP elevation, animals were killed and histologic counts of cells in the retinal ganglion cell (RGC) layer were made.RESULTS. Histologic measurements showed that, for animals with moderate elevation of IOP, memantine treatment was associated with an enhanced survival of RGCs in the inferior retina. Measurements of optic nerve head topography showed less IOP-induced change in memantine-treated animals. This effect was seen in measurements of both the cup and the neuroretinal rim. A comparison of these same histologic and morphologic measurements in normotensive eyes from the two treatment groups showed that memantine treatment was not associated with any significant effects on these eyes.CONCLUSIONS. Histologic measurements of RGC survival as well as tomographic measurements of nerve head topography show that systemic treatment with memantine, a compound which does not lower intraocular pressure, is both safe and effective to reduce changes associated with experimental glaucoma.