[关键词]
[摘要]
青光眼是以特征性视神经萎缩和视野缺损为共同特征的不可逆性致盲性眼病,高眼压是其最主要的发病机制,而导致高眼压的主要原因是房水传统流出途径中小梁网的病理学改变导致的房水流出阻力增加。Rho激酶抑制剂(ROCKi)是直接作用于小梁网(TM)的降眼压药物,主要通过影响细胞骨架改变TM细胞形态、细胞运动、胞质分裂和平滑肌收缩等,从而增加房水流出、降低眼压,在美国和日本已被批准用于临床; 具有改善视网膜血管灌注、促进视神经再生等作用,可能存在视神经保护作用; 此外,具有减少滤过泡瘢痕化等作用。因此,ROCKi作为新型抗青光眼药物备受关注,本文将针对Rho/Rho激酶信号通路、ROCKi的作用机制及其临床应用展开综述。
[Key word]
[Abstract]
Glaucoma is a leading cause of irreversible blindness, which is characterized by characteristic optic atrophy and visual field defects. Elevated intraocular pressure(IOP)is a primary risk factor of glaucoma, while the main cause of elevated IOP lies in the increased aqueous outflow resistance in pathological trabecular meshwork(TM), which is the conventional outflow pathway of aqueous humor. Rho-associated protein kinase inhibitor(ROCKi)is the IOP-lowering drug that is directly acting on the TM. The TM cell morphology, cell movement, cytokinesis and cell contraction by alteration of cytoskeleton can be changed by ROCKi to increase aqueous humor outflow facility and decrease IOP. ROCKi is now approved for clinical use in the United States and Japan. Meanwhile, it might play a role in optic nerve protection through increasing retinal vascular perfusion and promoting optic nerve regeneration. In addition, it decreases the possibility of filtration bleb scarring. Therefore, ROCKi has become a new pharmacological option to treat glaucoma. This article reviews the Rho-Rho kinase signaling pathway, the mechanism of ROCKi and its clinical application.
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[基金项目]
国家自然科学基金资助项目(No.81600726,81870653); 山东省自然科学基金资助项目(No.ZR2016HB53)