Ben Simon Guy J, Bakalash Sharon, Aloni Eyal, Rosner Mordechai
Department of Neurobiology, The Weizmann Institute of Science, Rehovot, Israel.
Am J Ophthalmol. 2006 Jun;141(6):1105-11. doi: 10.1016/j.ajo.2006.01.073.
To establish a rat model of acute increase in intraocular pressure (IOP) and to investigate the therapeutic window for protection against death of retinal ganglion cells (RGCs) by vaccination with glatiramer acetate (Cop-1) or by treatment with brimonidine or MK-801.
Animal study, laboratory investigation.
IOP was transiently increased in anesthetized Lewis rats by infusing normal saline (0.9%) into the anterior chamber of the eye for one hour. RGC survival was assessed one week and two weeks later by counting the RGCs retrogradely labeled with rhodamine dextran.
RGC survival.
IOP rose to 100 cm H(2)O (76 mm Hg) and returned to baseline after 24 hours. The RGC count decreased by 23% a week after the insult and by a further 7% after the second week. Vaccination with Cop-1 on the day of the insult prevented 50% of the IOP-induced RGC loss. Similar neuroprotection was achieved by daily intraperitoneal injections of brimonidine, but not with MK-801.
A transient increase in IOP to 100 cm H(2)O causes death of RGCs in rats. A single immunization with Cop-1 or daily injections of brimonidine protected up to 50% of potentially doomed RGCs from IOP-induced death, suggesting that not all of the cell death in the untreated model results from the IOP insult directly, but that some of it is caused by insult-induced environmental cytotoxicity, which is unrelated to glutamate toxicity or at least to NMDA receptors. These findings can be applied immediately as a basis for acute glaucoma therapy.
建立急性眼压升高的大鼠模型，研究通过醋酸格拉替雷（Cop-1）疫苗接种或使用溴莫尼定或MK-801治疗来保护视网膜神经节细胞（RGCs）免于死亡的治疗窗口。
动物研究，实验室调查。
通过向麻醉的Lewis大鼠眼前房内注入生理盐水（0.9%）1小时，使眼压短暂升高。在1周和2周后，通过计数用罗丹明葡聚糖逆行标记的RGCs来评估RGCs的存活情况。
RGCs存活情况。
眼压升至100 cm H₂O（76 mmHg），24小时后恢复至基线水平。损伤后1周RGC计数减少23%，第2周后又减少7%。在损伤当天接种Cop-1疫苗可预防50%的眼压诱导的RGC损失。每日腹腔注射溴莫尼定可获得类似的神经保护作用，但MK-801则无此作用。
眼压短暂升高至100 cm H₂O可导致大鼠RGCs死亡。单次接种Cop-1或每日注射溴莫尼定可保护高达50%可能注定死亡的RGCs免于眼压诱导的死亡，这表明在未治疗的模型中，并非所有细胞死亡都直接由眼压损伤引起，而是部分由损伤诱导的环境细胞毒性引起，这与谷氨酸毒性或至少与NMDA受体无关。这些发现可立即作为急性青光眼治疗的基础。
