Endogenous bioelectric currents promote differentiation of the mammalian lens

Research output: Contribution to journalArticle

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Abstract

The functional roles of bioelectrical signals (ES) created by the flow of specific ions at the mammalian lens equator are poorly understood. We detected that mature, denucleated lens fibers expressed high levels of the α1 and β1 subunits of Na+/K+ -ATPase (ATP1A1 and ATP1B1 of the sodium pump) and had a hyperpolarized membrane potential difference (Vmem). In contrast, differentiating, nucleated lens fiber cells had little ATP1A1 and ATP1B1 and a depolarized Vmem. Mimicking the natural equatorial ES with an applied electrical field (EF) induced a striking reorientation of lens epithelial cells to lie perpendicular to the direction of the EF. An EF also promoted the expression of β-crystallin, aquaporin-0 (AQP0) and the Beaded Filament Structural Protein 2 (BFSP2) in lens epithelial cells (LECs), all of which are hallmarks of differentiation. In addition, applied EF activated the AKT and CDC2 and inhibition of AKT reduced the activation of CDC2. Our results indicate that the endogenous bioelectrical signal at the lens equator promotes differentiation of LECs into denucleated lens fibre cells via depolarization of Vmem. Development of methods and devices of EF application or amplification in vivo may supply a novel treatment for lens diseases and even promote regeneration of a complete new lens following cataract surgery.
Original languageEnglish
Pages (from-to)2202-2212
Number of pages11
JournalJournal of Cellular Physiology
Volume233
Issue number3
Early online date30 Aug 2017
DOIs
Publication statusPublished - Mar 2018

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Lenses
Epithelial Cells
Lens Diseases
Fibers
Sodium-Potassium-Exchanging ATPase
Crystallins
Depolarization
Membrane Potentials
Cataract
Regeneration
Surgery
Amplification
Adenosine Triphosphatases
Ions
Chemical activation
Equipment and Supplies
Membranes

Keywords

  • ATP1B1
  • extracellular electrical signaling
  • lens epithelial cells
  • lens fiber
  • differentiation

Cite this

Endogenous bioelectric currents promote differentiation of the mammalian lens. / Cao, Lin; Liu, Jie; Pu, Jin; Collinson, J. Martin; Forrester, John V.; McCaig, Colin D.

In: Journal of Cellular Physiology, Vol. 233, No. 3, 03.2018, p. 2202-2212.

Research output: Contribution to journalArticle

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abstract = "The functional roles of bioelectrical signals (ES) created by the flow of specific ions at the mammalian lens equator are poorly understood. We detected that mature, denucleated lens fibers expressed high levels of the α1 and β1 subunits of Na+/K+ -ATPase (ATP1A1 and ATP1B1 of the sodium pump) and had a hyperpolarized membrane potential difference (Vmem). In contrast, differentiating, nucleated lens fiber cells had little ATP1A1 and ATP1B1 and a depolarized Vmem. Mimicking the natural equatorial ES with an applied electrical field (EF) induced a striking reorientation of lens epithelial cells to lie perpendicular to the direction of the EF. An EF also promoted the expression of β-crystallin, aquaporin-0 (AQP0) and the Beaded Filament Structural Protein 2 (BFSP2) in lens epithelial cells (LECs), all of which are hallmarks of differentiation. In addition, applied EF activated the AKT and CDC2 and inhibition of AKT reduced the activation of CDC2. Our results indicate that the endogenous bioelectrical signal at the lens equator promotes differentiation of LECs into denucleated lens fibre cells via depolarization of Vmem. Development of methods and devices of EF application or amplification in vivo may supply a novel treatment for lens diseases and even promote regeneration of a complete new lens following cataract surgery.",
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note = "Acknowledgements We are grateful to Kevin S. Mackenzie in our imaging core facility. This work was supported by the University of Aberdeen (at which the majority of the experimental work was conducted). The work was supported by Action Medical Research (GN2299) and Fight for Sight (RG13315-10).",
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N1 - Acknowledgements We are grateful to Kevin S. Mackenzie in our imaging core facility. This work was supported by the University of Aberdeen (at which the majority of the experimental work was conducted). The work was supported by Action Medical Research (GN2299) and Fight for Sight (RG13315-10).

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AB - The functional roles of bioelectrical signals (ES) created by the flow of specific ions at the mammalian lens equator are poorly understood. We detected that mature, denucleated lens fibers expressed high levels of the α1 and β1 subunits of Na+/K+ -ATPase (ATP1A1 and ATP1B1 of the sodium pump) and had a hyperpolarized membrane potential difference (Vmem). In contrast, differentiating, nucleated lens fiber cells had little ATP1A1 and ATP1B1 and a depolarized Vmem. Mimicking the natural equatorial ES with an applied electrical field (EF) induced a striking reorientation of lens epithelial cells to lie perpendicular to the direction of the EF. An EF also promoted the expression of β-crystallin, aquaporin-0 (AQP0) and the Beaded Filament Structural Protein 2 (BFSP2) in lens epithelial cells (LECs), all of which are hallmarks of differentiation. In addition, applied EF activated the AKT and CDC2 and inhibition of AKT reduced the activation of CDC2. Our results indicate that the endogenous bioelectrical signal at the lens equator promotes differentiation of LECs into denucleated lens fibre cells via depolarization of Vmem. Development of methods and devices of EF application or amplification in vivo may supply a novel treatment for lens diseases and even promote regeneration of a complete new lens following cataract surgery.

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