Aquaporin 0 Modulates Lens Gap Junctions in the Presence of Lens-Specific Beaded Filament Proteins.
Aquaporin 0 Modulates Lens Gap Junctions in the Presence of Lens-Specific Beaded Filament Proteins.
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DOI：
10.1167/iovs.17-22153
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发表时间：
2017-12-01
影响因子：
4.4
通讯作者：
Varadaraj K
中科院分区：
文献类型：
--
作者：
Kumari S;Gao J;Mathias RT;Sun X;Eswaramoorthy A;Browne N;Zhang N;Varadaraj K
本研究的目的是了解C57和FVB（缺乏珠状细丝[BF]）品系中发育的水通道蛋白0-敲除-杂合（AQP 0-Htz）小鼠中透镜白内障差异背后的分子和生理机制。使用暗场光学显微镜研究透镜透明度。在纤维细胞膜囊泡中测量水渗透性（Pf）。进行Western印迹/免疫染色以验证BF蛋白和连接蛋白的表达。测量基于微电极的完整透镜细胞内阻抗以确定间隙连接（GJ）耦合电阻。使用微电极/压力计系统测定透镜细胞内流体静压（HP）。FVB株AQP 0-Htz晶状体的透镜混浊度和球差比C57株晶状体明显。在任一背景下，与野生型（WT）相比，AQP 0-Htz晶状体显示Pf降低（约50%），其通过AQP 1的转基因表达（TgAQP 1/AQP 0-Htz）恢复，但FVB和C57之间的不透明和差异持续存在。Western印迹显示连接蛋白表达水平无变化。然而，在C57 AQP 0-Htz和TgAQP 1/AQP 0-Htz晶状体中，GJ耦合电阻降低约2.8倍，HP梯度降低约1.9倍。增加Pf在TgAQP 1/AQP 0-Htz没有改变GJ耦合电阻或HP。在C57 AQP 0-Htz透镜中，GJ耦合电阻降低。HP降低小于耦合阻力降低，反映了液体循环的增加，这是C57中白内障的严重程度低于FVB的原因之一。总体而言，我们的研究结果表明，AQP 0调节GJ在BF蛋白的存在下，以维持透镜的透明度和稳态。
The objective of this study was to understand the molecular and physiologic mechanisms behind the lens cataract differences in Aquaporin 0-knockout-Heterozygous (AQP0-Htz) mice developed in C57 and FVB (lacks beaded filaments [BFs]) strains. Lens transparency was studied using dark field light microscopy. Water permeability (Pf) was measured in fiber cell membrane vesicles. Western blotting/immunostaining was performed to verify expression of BF proteins and connexins. Microelectrode-based intact lens intracellular impedance was measured to determine gap junction (GJ) coupling resistance. Lens intracellular hydrostatic pressure (HP) was determined using a microelectrode/manometer system. Lens opacity and spherical aberration were more distinct in AQP0-Htz lenses from FVB than C57 strains. In either background, compared to wild type (WT), AQP0-Htz lenses showed decreased Pf (approximately 50%), which was restored by transgenic expression of AQP1 (TgAQP1/AQP0-Htz), but the opacities and differences between FVB and C57 persisted. Western blotting revealed no change in connexin expression levels. However, in C57 AQP0-Htz and TgAQP1/AQP0-Htz lenses, GJ coupling resistance decreased approximately 2.8-fold and the HP gradient decreased approximately 1.9-fold. Increased Pf in TgAQP1/AQP0-Htz did not alter GJ coupling resistance or HP. In C57 AQP0-Htz lenses, GJ coupling resistance decreased. HP reduction was smaller than the coupling resistance reduction, a reflection of an increase in fluid circulation, which is one reason for the less severe cataract in C57 than FVB. Overall, our results suggest that AQP0 modulates GJs in the presence of BF proteins to maintain lens transparency and homeostasis.
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