Aquaporin 0 Modulates Lens Gap Junctions in the Presence of Lens-Specific Beaded Filament Proteins
| Autor: | Junyuan Gao, Amizhdini Eswaramoorthy, Xiurong Sun, Nigel Zhang, Nicholas J Browne, Kulandaiappan Varadaraj, Richard T. Mathias, S. Sindhu Kumari |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Heterozygote cataractogenesis Genotype Blotting Western Hydrostatic pressure Connexin Aquaporin beaded filaments Cataract law.invention Protein filament Lens Mice 03 medical and health sciences Intermediate Filament Proteins law Lens Crystalline Electric Impedance Animals Eye Proteins transparency Mice Knockout Aquaporin 1 Aquaporin 0 Chemistry Gap junction Gap Junctions Mice Inbred C57BL Lens (optics) Disease Models Animal 030104 developmental biology Gene Expression Regulation Fiber cell Biophysics RNA sense organs Microelectrodes Intracellular |
| Zdroj: | Investigative Ophthalmology & Visual Science |
| ISSN: | 1552-5783 |
| DOI: | 10.1167/iovs.17-22153 |
| Popis: | Purpose 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. Methods 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. Results 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. Conclusions 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. |
| Databáze: | OpenAIRE |
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