title: Mechanical response of wild-type and Alport murine lens capsules during osmotic swelling.
abstract: The mechanical support of basement membranes, such as the lens capsule, is believed to arise from one of their main constituents - collagen IV. The basement membranes of the lens, kidney, and ear normally contain two different types of collagen IV networks, referred to as the major and minor chain networks. In Alport syndrome, a mutation in one of the minor chain COL4 genes leads to the absence of the minor chain network, causing life-threatening disturbances. We hypothesized that the absence of the minor chain network increases basement membrane distensibility, as measured in wild-type (n = 25) and Alport syndrome (n = 21) mice using the lens capsule as a model. Osmotic swelling experiments revealed direction-dependent changes. As a reflection of lens capsule properties, Alport lenses strained significantly more than wild-type lenses in the anterior-posterior direction, i.e. along their thickness, but not in the equatorial direction (p = 0.03 and p = 0.08, respectively). This is consistent with clinical data: Alport patients develop conical protrusions on the anterior and posterior lenticular poles. There was no evidence of significant change in total amount of collagen between Alport and wild-type lenses (p = 0.6). The observed differences in distensibility could indicate that the major chain network alone cannot fully compensate for the absence of the more highly cross-linked minor chain network, which is believed to be stronger, more stable, and resistant to deformation. The addition of mechanical information on Alport syndrome to the currently available biological data provides a fuller picture into the progression of the disease.
authors.affiliation: Department of Biomedical Engineering, University of Minnesota, 7-105 Nils Hasselmo Hall, 312 Church St. SE, Minneapolis, MN 55455, United States. gyone002@umn.edu
authors.forename: Lazarina
authors.initials: L
authors.lastname: Gyoneva
authors.forename: Yoav
authors.initials: Y
authors.lastname: Segal
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Dorfman
authors.forename: Victor H
authors.initials: VH
authors.lastname: Barocas
mesh_terms: D000818:Animals; D001485:Basement Membrane / Q000502:physiology*; D001696:Biomechanical Phenomena / Q000502:physiology; D018389:Codon, Nonsense / Q000235:genetics; D024141:Collagen Type IV / Q000235:genetics; D004548:Elasticity / Q000502:physiology*; D005838:Genotype; D007903:Lens Capsule, Crystalline / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009394:Nephritis, Hereditary / Q000235:genetics / Q000503:physiopathology*; D009995:Osmosis / Q000502:physiology*; D016133:Polymerase Chain Reaction; D014867:Water / Q000378:metabolism
chemical_list: D018389:Codon, Nonsense; C549554:Col4a5 protein, mouse; D024141:Collagen Type IV; D014867:Water
keywords: Alport syndrome; GBM; LC; biomechanics; collagen IV; glomerular basement membrane; lens capsule