Department of Ophthalmology, University of Tokyo, Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan.
Exp Eye Res. 2011 Sep;93(3):265-70. doi: 10.1016/j.exer.2011.06.022. Epub 2011 Jul 26.
Prostaglandin (PG) analogues may have an additional effect to protect neurons independent of IOP reduction. Only a few reports indicated that some PG analogues had neuroprotective effects or increased blood flow in in vivo and in vitro models. However, there is no comparative study using all clinically available PG analogues and also using primary culture of retinal ganglion cell (RGC). Our purpose of study is to investigate the direct neuroprotective effect of PG analogues on glutamate- and hypoxia-induced RGC death using rat purified primary RGC culture with latanoprost acid, travoprost acid, bimatoprost acid, bimatoprost, tafluprost acid, unoprostone, and PGF2α. Purified RGCs cultures were obtained from retinas of 6 days old Wistar rats, following a two-step immuno-panning procedure. After 72 h of cultivation, the neuroprotective effect of PG analogues (1 nM, 10 nM and 100 nM) was investigated by culturing the RGCs in 25 μM glutamate for a further 72 h or 5% O2 hypoxic condition for 24 h. The RGC viability under each condition normalized to that under normal condition without stress was evaluated as live cell percentage based on a total of 15 repeated experiments. As a result, 100 nM of latanoprost acid, tafluprost acid, bimatoprost acid, and bimatoprost significantly increased RGC survival rate by suppressing apoptosis. PG analogues indicated IOP independent neuroprotective effect on glutamate- or hypoxia-induced RGC death using rat primary RGC culture at clinically available intracameral concentration. Since those profiles were different from clinical efficacy in IOP reduction, the mechanism of neuroprotection may be not related to FP receptor stimulation.
前列腺素（PG）类似物可能具有独立于眼压降低的额外神经元保护作用。只有少数报道表明，一些 PG 类似物具有神经保护作用或增加了在体和体外模型中的血流。然而，目前还没有使用所有临床可用的 PG 类似物并使用视网膜神经节细胞（RGC）原代培养物进行的比较研究。我们的研究目的是使用拉坦前列素酸、曲伏前列素酸、贝美前列素酸、贝美前列素、他氟前列素酸、乌诺前列酮和 PGF2α，用鼠纯化的原代 RGC 培养物来研究 PG 类似物对谷氨酸和缺氧诱导的 RGC 死亡的直接神经保护作用。通过两步免疫淘选程序从 6 天大的 Wistar 大鼠视网膜中获得纯化的 RGC 培养物。培养 72 小时后，将 RGC 在 25 μM 谷氨酸中进一步培养 72 小时或在 5% O2 缺氧条件下培养 24 小时，以研究 PG 类似物（1 nM、10 nM 和 100 nM）的神经保护作用。在每种条件下的 RGC 活力与无应激的正常条件下的活力归一化，根据总共 15 次重复实验，评估为活细胞百分比。结果，100 nM 的拉坦前列素酸、他氟前列素酸、贝美前列素酸和贝美前列素通过抑制细胞凋亡显著增加了 RGC 的存活率。PG 类似物在临床可用的房水浓度下，对谷氨酸或缺氧诱导的 RGC 死亡具有独立于眼压的神经保护作用，这表明在使用鼠原代 RGC 培养物的情况下，PG 类似物具有独立于眼压的神经保护作用。由于这些作用模式与眼压降低的临床疗效不同，神经保护的机制可能与 FP 受体刺激无关。
