Mechanical response of wild-type and Alport murine lens capsules during osmotic swelling

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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.

Original languageEnglish (US)
Pages (from-to)87-91
Number of pages5
JournalExperimental Eye Research
Volume113
DOIs
StatePublished - Aug 2013

Bibliographical note

Funding Information:
We thank Sandy Johnson for her technical expertise in performing the collagen assay and Dr. William Thomas for his advice and guidance on the statistical analysis. L.G. was supported by a National Science Foundation Graduate Research Fellowship . This work was supported with resources and the use of facilities at the Minneapolis VA Health Care System and the University of Minnesota Institute for Engineering in Medicine.

Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.

Keywords

  • Alport syndrome
  • Biomechanics
  • Collagen IV
  • Glomerular basement membrane
  • Lens capsule

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