Rao Vasantha P, Epstein David L
Department of Ophthalmology, Duke University School of Medicine, Durham, North Carolina, USA.
BioDrugs. 2007;21(3):167-77. doi: 10.2165/00063030-200721030-00004.
Rho kinase (ROCK1 and ROCK2) is a serine/threonine kinase that serves as an important downstream effector of Rho GTPase, and plays a critical role in regulating the contractile tone of smooth muscle tissues in a calcium-independent manner. Several lines of experimental evidence indicate that modulating ROCK activity within the aqueous humor outflow pathway using selective inhibitors could achieve very significant benefits for the treatment of increased intraocular pressure in patients with glaucoma. The rationale for such an approach stems from experimental data suggesting that both ROCK and Rho GTPase inhibitors can increase aqueous humor drainage through the trabecular meshwork, leading to a decrease in intraocular pressure. In addition to their ocular hypotensive properties, inhibitors of both ROCK and Rho GTPase have been shown to enhance ocular blood flow, retinal ganglion cell survival and axon regeneration. These properties of the ROCK and Rho GTPase inhibitors indicate that targeting the Rho GTPase/ROCK pathway with selective inhibitors represents a novel therapeutic approach aimed at lowering increased intraocular pressure in glaucoma patients.
Rho激酶（ROCK1和ROCK2）是一种丝氨酸/苏氨酸激酶，作为Rho GTP酶的重要下游效应器，以不依赖钙的方式在调节平滑肌组织的收缩张力中起关键作用。多项实验证据表明，使用选择性抑制剂调节房水流出途径中的ROCK活性，对于治疗青光眼患者眼内压升高可能会带来非常显著的益处。这种方法的理论依据源于实验数据，表明ROCK和Rho GTP酶抑制剂均可增加房水通过小梁网的引流，从而导致眼内压降低。除了具有降眼压特性外，ROCK和Rho GTP酶抑制剂还被证明可增强眼部血流、视网膜神经节细胞存活及轴突再生。ROCK和Rho GTP酶抑制剂的这些特性表明，用选择性抑制剂靶向Rho GTP酶/ROCK途径代表了一种旨在降低青光眼患者升高的眼内压的新型治疗方法。
