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

目的：目的：研究抗青光眼滴眼液对N-甲基-D-天冬氨酸（NMDA）诱导的视网膜损伤及眼表的影响。用几种抗青光眼滴眼液、β-受体阻滞剂、α/β-受体阻滞剂、α_1受体阻滞剂、α_2受体激动剂和前列腺素衍生物局部给药于NMDA处理的大鼠眼和未处理的大鼠眼，观察视网膜厚度、逆行标记视网膜神经节细胞（RGC）数量、结果：玻璃体内注射NMDA可使视网膜层厚度明显减少，并诱导胶质细胞增生蛋白（GFAP）表达上调。局部给予β受体阻滞剂和前列腺素衍生物对视网膜厚度、RGCs数量或GFAP表达几乎没有显著影响。而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RGCs数量有保护作用，并能显著抑制NMDA诱导的GFAP表达上调。在1101个与细胞调节机制相关的基因中，胰岛素样生长因子IGF-1和ErbB 3的两个基因的表达在α/β阻断剂、α_1阻断剂和α_2激动剂给药后发生改变。结论：抗青光眼滴眼液通过调节α肾上腺素能受体（α 1受体阻滞剂和α 2受体激动剂），对NMDA诱导的大鼠视网膜损伤具有保护作用。α/β受体阻滞剂、α_1受体阻滞剂和前列腺素衍生物可诱导ECM降解，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.