Study of effects of antiglaucoma eye drops on glaucomatous optic neuropathy and ocular serface.

目的：研究抗青光眼滴眼液对N-甲基-D-天冬氨酸(N-甲基-D-aspartate，N-甲基-D-天冬氨酸)诱导的大鼠视网膜损伤和眼表的影响。方法：用抗青光眼滴眼液、β阻滞剂、α/β阻滞剂、α_1阻滞剂、α_2激动剂和前列腺素衍生物对N-甲基-D-天冬氨酸治疗的大鼠和非治疗大鼠的视网膜厚度、逆行标记的视网膜神经节细胞(RGC)数、基因芯片分析结果进行比较。结果：玻璃体内注射NMDA后，视网膜各层厚度明显减少，胶质纤维蛋白(GFAP)表达上调。局部应用β阻滞剂和前列腺素衍生物对视网膜厚度、视网膜节细胞数量或胶质纤维酸性蛋白表达几乎没有显著影响。α/β受体阻滞剂、α_1受体阻滞剂和α_2受体激动剂对视网膜厚度和视网膜神经节细胞数有明显的保护作用，并能明显抑制α诱导的胶质纤维酸性蛋白表达上调。在与细胞调控机制相关的1101个基因中，胰岛素样生长因子IGF-1和ErbB3两个基因的表达在给予α/β阻滞剂、α_1阻滞剂和α_2激动剂后发生了变化。此外，局部应用α/β受体阻滞剂、α_1阻滞剂和前列腺素衍生物可诱导结膜基质金属蛋白酶表达上调，结膜基质金属抑制蛋白表达下调。结论：抗青光眼滴眼液对α肾上腺素能受体、α_1阻断和α_2刺激的调节可能对NMDA性视网膜损伤有一定的保护作用。我们的结果还表明，α/β阻滞剂、α_1阻滞剂和前列腺素衍生物可诱导细胞外基质的降解，从而影响滤过手术。

Purpose : To study the effects of antiglaucoma eye drops on N-methyl-D-aspartate (NMDA)-induced retinal damage and ocular surfaceMethods : Several antiglaucoma eye drops, β-blockers, α/β-blockers, an α_1-blocker, and α_2-agonist, and a prostaglandin derivative, were topically administrated to NMDA-treated rat eyes or non-treated rat eye, and the retinal thickness, the number of retrograde-labeled retinal ganglion cells (RGCs), the results of a cDNA microarray analysis, and the levels of matrix metalloprotease (MMP) and tissue inhibitor of matrix protease (TIMP) which regulate the metabolism of the extracellular matrix (ECM) were studied.Results : Intravitreal administration of NMDA caused a significant decrease in the thickness of the retinal layers and induced upregulation of glial fibrillary protein (GFAP). Topical administration of β-blockers and a prostaglandin derivative showed almost no significant effects on retinal thickness, the number of RGCs, or expression of GFAP. In contrast, the α/β-blockers, the α_1-blocker, and the α_2-agonist showed preservation effects on retinal thickness and the the number of RGCs, and marked suppression of NMDA-induced upregulation of GFAP. Among 1101 genes related to cellular regulatory mechanisms, the expression of two genes, both for insulin-like growth factors, IGF-1 and ErbB3,was altered upon administration of the α/β-blockers, the α_1-blocker, and the α_2-agonist. In addition, topical administration of the α/β-blockers, the α_1-blocker, and the prostaglandin derivative induced upregulation of MMP and downregulation of TIMP of conjunctiva.Conclusion : Our present study suggests that modulations of the α-adrenergic receptor, α_1-blocking, and α_2-stimulation, by antiglaucoma eye drops may cause beneficial effects on NMDA-induced retinal damage in the rat. Our results also suggests that the α/β-blockers, the α_1-blocker, and the prostaglandin derivative induce degradation of ECM, affcting filter surgery.