Aquaporin 0 plays a pivotal role in refractive index gradient development in mammalian eye lens to prevent spherical aberration.
Aquaporin 0 plays a pivotal role in refractive index gradient development in mammalian eye lens to prevent spherical aberration.
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DOI：
10.1016/j.bbrc.2014.09.032
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发表时间：
2014-10-03
影响因子：
3.1
通讯作者：
Varadaraj, Kulandaiappan
中科院分区：
文献类型：
--
作者：
Kumari, S. Sindhu;Varadaraj, Kulandaiappan
水通道蛋白0 （AQP0）是一种跨膜通道，约占哺乳动物晶状体纤维细胞膜蛋白总量的45%。当基因突变和基因敲除导致常染色体显性晶状体白内障时，它对晶状体透明和体内平衡至关重要。AQP0在晶状体中作为水通道和细胞间粘附（CTCA）分子。我们最近的体外研究表明AQP0的CTCA功能可能对晶状体折射率梯度（RING）的建立至关重要。然而，缺乏体内数据来证实AQP0作为一种纤维CTCA分子的作用，而这种分子对于透镜环的形成至关重要。本研究旨在收集AQP0参与晶状体环发育的体内证据。采用野生型（WT）小鼠晶状体、AQP0敲除（杂合子、AQP0+/−）和AQP0敲除转基因表达AQP1（杂合子AQP0+/−/AQP1+/−）小鼠模型。通过MALDI-TOF质谱和SDS-PAGE对晶体中完整AQP0和N-和/或c端断裂AQP0蛋白谱的分析发现，皮层外纤维细胞只有~28 kDa的完整AQP0，皮层内和核外纤维细胞既有完整AQP0，也有断裂AQP0，核内纤维细胞只有断裂AQP0 （~26 - 24kDa）。敲除50% AQP0蛋白引起光散射、球差（SA）和白内障。转基因AQP1恢复失去的纤维细胞膜透水性（Pf）并没有恢复晶状体完全透明，小鼠晶状体出现光散射和SA。两种小鼠模型的晶状体透射电镜和扫描电镜显示纤维细胞之间的细胞外空间增加。水含量测定研究表明，这些小鼠模型的晶状体中水含量增加。综上所述，晶状体透明度、CTCA和纤维细胞致密性受到影响，这可能是由于50% AQP0的损失导致细胞外空间变大、含水量和SA增加，这可能是由于RING的改变。据我们所知，这是首次发现AQP0在RING发育中防止聚焦过程中晶状体SA的作用。
Aquaporin 0 (AQP0) is a transmembrane channel that constitutes ~45% of the total membrane protein of the fiber cells in mammalian lens. It is critical for lens transparency and homeostasis as mutations and knockout cause autosomal dominant lens cataract. AQP0 functions as a water channel and as a cell-to-cell adhesion (CTCA) molecule in the lens. Our recent in vitro studies showed that the CTCA function of AQP0 could be crucial to establish lens refractive index gradient (RING). However, there is a lack of in vivo data to corroborate the role of AQP0 as a fiber CTCA molecule which is critical for creating lens RING. The present investigation is undertaken to gather in vivo evidence for the involvement of AQP0 in developing lens RING. Lenses of wild type (WT) mouse, AQP0 knockout (heterozygous, AQP0+/−) and AQP0 knockout lens transgenically expressing AQP1 (heterozygous AQP0+/−/AQP1+/−) mouse models were used for the study. Data on AQP0 protein profile of intact and N- and/or C-terminal cleaved AQP0 in the lens by MALDI-TOF mass spectrometry and SDS-PAGE revealed that outer cortex fiber cells have only intact AQP0 of ~28 kDa, inner cortical and outer nuclear fiber cells have both intact and cleaved forms, and inner nuclear fiber cells have only cleaved forms (~26 - 24kDa). Knocking out of 50% of AQP0 protein caused light scattering, spherical aberration (SA) and cataract. Restoring the lost fiber cell membrane water permeability (Pf) by transgene AQP1 did not reinstate complete lens transparency and the mouse lenses showed light scattering and SA. Transmission and scanning electron micrographs of lenses of both mouse models showed increased extracellular space between fiber cells. Water content determination study showed increase in water in the lenses of these mouse models. In summary lens transparency, CTCA and compact packing of fiber cells were affected due to the loss of 50% AQP0 leading to larger extracellular space, more water content and SA, possibly due to alteration in RING. To our knowledge, this is the first report identifying the role of AQP0 in RING development to ward off lens SA during focusing.
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影响因子：
3.9
作者：
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通讯作者：
Pierscionek, BK
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