Role of Aquaporin 0 in lens biomechanics

S. Sindhu Kumari, Neha Gupta, Alan Shiels, Paul G FitzGerald, Anil G. Menon, Richard T. Mathias, Kulandaiappan Varadaraj

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Abstract Maintenance of proper biomechanics of the eye lens is important for its structural integrity and for the process of accommodation to focus near and far objects. Several studies have shown that specialized cytoskeletal systems such as the beaded filament (BF) and spectrin-actin networks contribute to mammalian lens biomechanics; mutations or deletion in these proteins alters lens biomechanics. Aquaporin 0 (AQP0), which constitutes ∼45% of the total membrane proteins of lens fiber cells, has been shown to function as a water channel and a structural cell-to-cell adhesion (CTCA) protein. Our recent ex vivo study on AQP0 knockout (AQP0 KO) mouse lenses showed the CTCA function of AQP0 could be crucial for establishing the refractive index gradient. However, biomechanical studies on the role of AQP0 are lacking. The present investigation used wild type (WT), AQP5 KO (AQP5<sup>-/-</sup>), AQP0 KO (heterozygous KO: AQP0<sup>+/-</sup>; homozygous KO: AQP0<sup>-/-</sup>; all in C57BL/6J) and WT-FVB/N mouse lenses to learn more about the role of fiber cell AQPs in lens biomechanics. Electron microscopic images exhibited decreases in lens fiber cell compaction and increases in extracellular space due to deletion of even one allele of AQP0. Biomechanical assay revealed that loss of one or both alleles of AQP0 caused a significant reduction in the compressive load-bearing capacity of the lenses compared to WT lenses. Conversely, loss of AQP5 did not alter the lens load-bearing ability. Compressive load-bearing at the suture area of AQP0<sup>+/-</sup> lenses showed easy separation while WT lens suture remained intact. These data from KO mouse lenses in conjunction with previous studies on lens-specific BF proteins (CP49 and filensin) suggest that AQP0 and BF proteins could act co-operatively in establishing normal lens biomechanics. We hypothesize that AQP0, with its prolific expression at the fiber cell membrane, could provide anchorage for cytoskeletal structures like BFs and together they help to confer fiber cell shape, architecture and integrity. To our knowledge, this is the first report identifying the involvement of an aquaporin in lens biomechanics. Since accommodation is required in human lenses for proper focusing, alteration in the adhesion and/or water channel functions of AQP0 could contribute to presbyopia.

Original languageEnglish (US)
Article number33884
Pages (from-to)339-345
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume462
Issue number4
DOIs
StatePublished - Apr 19 2015

Fingerprint

Biomechanics
Biomechanical Phenomena
Lenses
Aquaporins
Weight-Bearing
Bearings (structural)
Fibers
aquaporin 0
Cell adhesion
Cell Adhesion
Sutures
Alleles
Presbyopia
Proteins
Spectrin
Refractometry
Crystalline Lens
Crystallins
Cell Shape
Sequence Deletion

Keywords

  • Accommodation
  • AQP0
  • CP49
  • Filensin
  • Lens biomechanics
  • Presbyopia

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

Cite this

Sindhu Kumari, S., Gupta, N., Shiels, A., FitzGerald, P. G., Menon, A. G., Mathias, R. T., & Varadaraj, K. (2015). Role of Aquaporin 0 in lens biomechanics. Biochemical and Biophysical Research Communications, 462(4), 339-345. [33884]. https://doi.org/10.1016/j.bbrc.2015.04.138

Role of Aquaporin 0 in lens biomechanics. / Sindhu Kumari, S.; Gupta, Neha; Shiels, Alan; FitzGerald, Paul G; Menon, Anil G.; Mathias, Richard T.; Varadaraj, Kulandaiappan.

In: Biochemical and Biophysical Research Communications, Vol. 462, No. 4, 33884, 19.04.2015, p. 339-345.

Research output: Contribution to journalArticle

Sindhu Kumari, S, Gupta, N, Shiels, A, FitzGerald, PG, Menon, AG, Mathias, RT & Varadaraj, K 2015, 'Role of Aquaporin 0 in lens biomechanics', Biochemical and Biophysical Research Communications, vol. 462, no. 4, 33884, pp. 339-345. https://doi.org/10.1016/j.bbrc.2015.04.138
Sindhu Kumari S, Gupta N, Shiels A, FitzGerald PG, Menon AG, Mathias RT et al. Role of Aquaporin 0 in lens biomechanics. Biochemical and Biophysical Research Communications. 2015 Apr 19;462(4):339-345. 33884. https://doi.org/10.1016/j.bbrc.2015.04.138
Sindhu Kumari, S. ; Gupta, Neha ; Shiels, Alan ; FitzGerald, Paul G ; Menon, Anil G. ; Mathias, Richard T. ; Varadaraj, Kulandaiappan. / Role of Aquaporin 0 in lens biomechanics. In: Biochemical and Biophysical Research Communications. 2015 ; Vol. 462, No. 4. pp. 339-345.
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