Gao Junyuan, Sun Xiurong, White Thomas W, Delamere Nicholas A, Mathias Richard T
Department of Physiology and Biophysics, Stony Brook University, Stony Brook, New York.
Department of Physiology and Biophysics, University of Arizona, Tucson, Arizona.
Biophys J. 2015 Nov 3;109(9):1830-9. doi: 10.1016/j.bpj.2015.09.018.
In wild-type lenses from various species, an intracellular hydrostatic pressure gradient goes from ∼340 mmHg in central fiber cells to 0 mmHg in surface cells. This gradient drives a center-to-surface flow of intracellular fluid. In lenses in which gap-junction coupling is increased, the central pressure is lower, whereas if gap-junction coupling is reduced, the central pressure is higher but surface pressure is always zero. Recently, we found that surface cell pressure was elevated in PTEN null lenses. This suggested disruption of a feedback control system that normally maintained zero surface cell pressure. Our purpose in this study was to investigate and characterize this feedback control system. We measured intracellular hydrostatic pressures in mouse lenses using a microelectrode/manometer-based system. We found that all feedback went through transport by the Na/K ATPase, which adjusted surface cell osmolarity such that pressure was maintained at zero. We traced the regulation of Na/K ATPase activity back to either TRPV4, which sensed positive pressure and stimulated activity, or TRPV1, which sensed negative pressure and inhibited activity. The inhibitory effect of TRPV1 on Na/K pumps was shown to signal through activation of the PI3K/AKT axis. The stimulatory effect of TRPV4 was shown in previous studies to go through a different signal transduction path. Thus, there is a local two-legged feedback control system for pressure in lens surface cells. The surface pressure provides a pedestal on which the pressure gradient sits, so surface pressure determines the absolute value of pressure at each radial location. We speculate that the absolute value of intracellular pressure may set the radial gradient in the refractive index, which is essential for visual acuity.
在来自不同物种的野生型晶状体中，细胞内静水压力梯度从中央纤维细胞中的约340 mmHg降至表面细胞中的0 mmHg。这种梯度驱动细胞内液从中心向表面流动。在缝隙连接耦合增加的晶状体中，中央压力较低，而如果缝隙连接耦合减少，中央压力较高，但表面压力始终为零。最近，我们发现PTEN基因敲除的晶状体中表面细胞压力升高。这表明通常维持表面细胞压力为零的反馈控制系统受到了破坏。我们在本研究中的目的是调查和表征这种反馈控制系统。我们使用基于微电极/压力计的系统测量了小鼠晶状体中的细胞内静水压力。我们发现所有反馈都通过Na/K ATP酶的转运来实现，该酶调节表面细胞渗透压，从而使压力维持在零。我们将Na/K ATP酶活性的调节追溯到TRPV4，它感知正压并刺激活性，或者追溯到TRPV1，它感知负压并抑制活性。TRPV1对Na/K泵的抑制作用通过PI3K/AKT轴的激活来发出信号。TRPV4的刺激作用在先前的研究中表明是通过不同的信号转导途径实现的。因此，晶状体表面细胞压力存在一个局部的双足反馈控制系统。表面压力提供了一个压力梯度所依赖的基座，所以表面压力决定了每个径向位置的压力绝对值。我们推测细胞内压力的绝对值可能设定了折射率的径向梯度，这对视力至关重要。
