eNOS, a Pressure-Dependent Regulator of Intraocular Pressure
eNOS, a Pressure-Dependent Regulator of Intraocular Pressure
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DOI：
10.1167/iovs.11-7839
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发表时间：
2011-12-01
影响因子：
4.4
通讯作者：
Ethier, C. Ross
中科院分区：
文献类型：
--
作者：
Stamer, W. Daniel;Lei, Yuan;Ethier, C. Ross
目的.眼内房水主要引流途径的病理学是导致高眼压的原因，高眼压是青光眼患者唯一可治疗的风险因素。不幸的是，调节压力依赖性房水引流并因此调节眼内压（IOP）的机制尚不清楚。为了更好地了解一种可能的潜在的分子因子，调节眼压，一氧化氮（NO），压力依赖性引流在转基因小鼠过表达内皮NO合酶（eNOS）进行了研究。在小鼠中通过回弹眼压测量法测量IOP，并且使用模拟AH +/-100 μ M L-NAME，在8和45 mm Hg之间的多个压力下通过离体灌注测量压力与流量数据。使用标准技术对一部分眼睛进行组织学检查，或通过蛋白质印迹分析测定融合蛋白表达。结果。眼压较低（9.6 +/- 2.7 vs. 11.4 +/- 2.5 mm Hg;平均值+/- SD; P = 0.04），压力依赖性引流更高（0.0154 +/- 0.006 vs. 0.0066 +/- 0.0009 mu L/min/mm Hg; P = 0.002）;然而，非压力依赖性引流未受影响。NOS抑制剂L-NAME使转基因动物的压力依赖性引流正常化。对于IOP > 35 mm Hg，野生型小鼠中的压力-流量曲线的斜率增加以匹配在转基因小鼠中观察到的斜率。在升高的压力下，压力依赖性通路中的剪切应力被计算为在已知影响血管内皮中eNOS表达和活性的范围内。内皮NOS过度表达通过增加小鼠眼内压力依赖性引流降低IOP。数据与NO在房水动力学中具有机械调节作用一致，其中在升高的IOP下eNOS诱导导致增加的压力依赖性流出。（Invest Ophthalmol维斯科学。2011; 52：9438-9444）DOI：10.1167/iovs.11-7839
PURPOSE. Pathology in the primary drainage pathway for aqueous humor in the eye is responsible for ocular hypertension, the only treatable risk factor in patients with glaucoma. Unfortunately, the mechanisms that regulate pressure-dependent drainage of aqueous humor and thus intraocular pressure (IOP) are unknown. To better understand one possible underlying molecular factor that regulates IOP, nitric oxide (NO), pressure-dependent drainage in transgenic mice overexpressing endothelial NO synthase (eNOS) was studied.METHODS. IOP was measured by rebound tonometry in mice, and pressure versus flow data were measured by ex vivo perfusion at multiple pressures between 8 and 45 mm Hg, using mock AH +/- 100 mu M L-NAME. A subset of eyes was examined histologically using standard techniques or was assayed for fusion protein expression by Western blot analysis.RESULTS. IOP was lower (9.6 +/- 2.7 vs. 11.4 +/- 2.5 mm Hg; mean +/- SD; P = 0.04) and pressure-dependent drainage was higher (0.0154 +/- 0.006 vs. 0.0066 +/- 0.0009 mu L/min/mm Hg; P = 0.002) in the transgenic mice than in the wild-type animals; however, pressure-independent drainage was unaffected. The NOS inhibitor L-NAME normalized pressure-dependent drainage in transgenic animals. For IOP > 35 mm Hg, the slope of the pressure-flow curve in wild-type mice increased to match that seen in transgenic mice. Shear stress in the pressure-dependent pathway at elevated pressures was calculated to be in a range known to affect eNOS expression and activity in vascular endothelia.CONCLUSIONS. Endothelial NOS overexpression lowers IOP by increasing pressure-dependent drainage in the mouse eye. Data are consistent with NO's having a mechanoregulatory role in aqueous humor dynamics, with eNOS induction at elevated IOPs leading to increased pressure-dependent outflow. (Invest Ophthalmol Vis Sci. 2011; 52: 9438-9444) DOI: 10.1167/iovs.11-7839