Lens transcriptome profile during cataract development in Mip-null mice

Thomas M. Bennett, Yuefang Zhou, Alan Shiels

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Major intrinsic protein or aquaporin-0 (MIP/AQP0) functions as a water channel and a cell-junction molecule in the vertebrate eye lens. Loss of MIP function in the lens leads to degraded optical quality and cataract formation by pathogenic mechanisms that are unclear. Here we have used microarray-hybridization analysis to detect lens transcriptome changes during cataract formation in mice that are functionally null for MIP (Mip−/−). In newborn Mip−/− lenses (P1) 11 genes were up-regulated and 18 were down-regulated (>2-fold, p=<0.05) and a similar number of genes was differentially regulated at P7. The most up-regulated genes (>6-fold) in the Mip−/− lens at P1 included those coding for a mitochondrial translocase (Timmdc1), a matrix metallopeptidase (Mmp2), a Rho GTPase-interacting protein (Ubxn11) and a transcription factor (Twist2). Apart from Mip, the most down-regulated genes (>4-fold) in the Mip−/− lens at P1 included those coding for a proteasome sub-unit (Psmd8), a ribonuclease (Pop4), and a heat-shock protein (Hspb1). Lens fiber cell degeneration in the Mip−/− lens was associated with increased numbers of TUNEL-positive cell nuclei and dramatically elevated levels of calpain-mediated proteolysis of αII-spectrin. However red-ox status, measured by glutathione and free-radical levels, was similar to that of wild-type. These data suggest that while relatively few genes (∼1.5% of the transcriptome) were differentially regulated >2-fold in the Mip−/− lens, calpain hyper-activation acts as a terminal pathogenic event during lens fiber cell death and cataract formation.

Original languageEnglish
Pages (from-to)988-993
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume478
Issue number2
DOIs
StatePublished - Sep 16 2016

Keywords

  • Aquaporin-0
  • Calpain
  • Cataract
  • Hspb1
  • Lens
  • Transcriptome

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