Müller细胞反应性胶质化在急性高眼压致大鼠视网膜损伤中作用

Role of Müller cell-specific reactive gliosis in acute ocular hypertension-induced retinal damage of rats

目的观察Müller细胞反应性胶质化在急性高眼压(AOH)大鼠视网膜中变化及其抑制对视网膜损伤的影响。方法建立大鼠AOH青光眼模型,分为正常对照(Ctrl)、AOH和AOH+玻璃体内注射胶质毒素α-氨基己二酸(AAA)后再灌注1、3和5d组,以及单纯AAA和AOH+PBS对照组。TUNEL染色检测细胞凋亡,GFAP免疫荧光染色反应Müller细胞反应性胶质化程度,Thy-1染色标记视网膜神经节细胞(RGCs)。结果 AOH可致大鼠视网膜内丛状层和内核层明显变薄、神经节细胞层内细胞排列紊乱和数量减少,并诱发Müller细胞反应性胶质化(GFAP表达增加)。同时,AAA抑制Müller细胞反应性胶质化可明显缓解AOH所致RGCs丢失和凋亡发生。结论 Müller细胞反应性胶质化参与AOH所致视网膜损伤,抑制其反应性胶质化可能是改善高眼压性青光眼视网膜病变的一种有效治疗方法。

Objective To observe Mtiller cell-specific reactive gliosis in rat retina following acute ocular hyperten- sion （AOH） and its effect on AOH-induced retinal damage. Methods The AOH rat model was established, and the animals were divided into control （ Ctrl）, AOH and AOH ＋ ot-aminoadipic acid （ AAA, intravitreal injection） treated groups （1, 3 and 5d subgroups according the reperfusion time）, AAA treatment or AOH ＋ PBS control group. TUNEL assay was used to detect cell apoptosis, GFAP immunofluorescent staining was performed to respond Miiller cell-specific reactive gliosis, and Thy-1 staining was applied to mark retinal ganglion cells （RGCs）. Results AOH attenuated the thicknesses of inner plexiform layer （IPL） and inner nuclear layer （INL）, and cause cell disorganization and cell loss in ganglion cell layer （GCL） as well as the Müller cell-specific reactive gliosis （en- hanced GFAP-immunoreactivity） in rat retina. In addition, the inhibition of Müller cell-specific reactive gliosis by AAA intravitreal injection did significantly relief RGCs loss and cell apoptosis in GCL layer of AOH rat retina.Conclusions Müller cell-specific reactive gliosis is involved in AOH-induced retinal damage and its inhibition may be a potential therapeutic strategy for improving glaucomatous retinopathy.