title: Role of Aquaporin 0 in lens biomechanics.
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(-/-)), AQP0 KO (heterozygous KO: AQP0(+/-); homozygous KO: AQP0(-/-); 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(+/-) 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.
authors.affiliation: Physiology and Biophysics, Stony Brook University, Stony Brook, NY, USA.
authors.forename: S
authors.initials: S
authors.lastname: Sindhu Kumari
authors.affiliation: Physiology and Biophysics, Stony Brook University, Stony Brook, NY, USA.
authors.forename: Neha
authors.initials: N
authors.lastname: Gupta
authors.affiliation: Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Alan
authors.initials: A
authors.lastname: Shiels
authors.affiliation: Cell Biology and Human Anatomy, School of Medicine, University of California, Davis, CA, USA.
authors.forename: Paul G
authors.initials: PG
authors.lastname: FitzGerald
authors.affiliation: University of Cincinnati College of Medicine, Cincinnati, OH, USA.
authors.forename: Anil G
authors.initials: AG
authors.lastname: Menon
authors.affiliation: Physiology and Biophysics, Stony Brook University, Stony Brook, NY, USA; SUNY Eye Institute, NY, USA.
authors.forename: Richard T
authors.initials: RT
authors.lastname: Mathias
authors.affiliation: Physiology and Biophysics, Stony Brook University, Stony Brook, NY, USA; SUNY Eye Institute, NY, USA. Electronic address: kulandaiappan.varadaraj@stonybrook.edu.
authors.forename: Kulandaiappan
authors.initials: K
authors.lastname: Varadaraj
mesh_terms: D000818:Animals; D020346:Aquaporins / Q000502:physiology*; D001696:Biomechanical Phenomena; D005136:Eye Proteins / Q000502:physiology*; D007908:Lens, Crystalline / Q000502:physiology* / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D008855:Microscopy, Electron, Scanning; D016133:Polymerase Chain Reaction
chemical_list: D020346:Aquaporins; D005136:Eye Proteins; C030328:aquaporin 0
keywords: AQP0; Accommodation; CP49; Filensin; Lens biomechanics; Presbyopia