April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
Anterior Plaque Formation Phenotype Linked to Activation of Aldose Reductase (AKR1B1)
Author Affiliations & Notes
  • P. A. Ruzycki
    Rocky Mt Lions Eye Inst/Ophthalmology, Univ of Colorado, Denver Hlth Sci Ctr, Aurora, Colorado
  • G. J. Zablocki
    Rocky Mt Lions Eye Inst/Ophthalmology, Univ of Colorado, Denver Hlth Sci Ctr, Aurora, Colorado
  • S. Palla
    Biochemistry, National Institute of Nutrition, Hyderabad, India
  • D. A. Ammar
    Rocky Mt Lions Eye Inst/Ophthalmology, Univ of Colorado, Denver Hlth Sci Ctr, Aurora, Colorado
  • B. G. Reddy
    Biochemistry, National Institute of Nutrition, Hyderabad, India
  • J. M. Petrash
    Rocky Mt Lions Eye Inst/Ophthalmology, Univ of Colorado, Denver Hlth Sci Ctr, Aurora, Colorado
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 2623. doi:
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    • Get Citation

      P. A. Ruzycki, G. J. Zablocki, S. Palla, D. A. Ammar, B. G. Reddy, J. M. Petrash; Anterior Plaque Formation Phenotype Linked to Activation of Aldose Reductase (AKR1B1). Invest. Ophthalmol. Vis. Sci. 2010;51(13):2623.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : Transgenic mice that express high levels of human aldose reductase (AKR1B1) develop an unusual phenotype consistent with aberrant differentiation of lens epithelial cells. The purpose of this study was to characterize this phenotype and to probe the role of activated aldose reductase in mediating abnormal differentiation of epithelial cells.

Methods: : Lenses were obtained from AKR1B1 transgenic mouse strains and nontransgenic controls. Immunofluorescence and H&E staining were used to characterize and evaluate lens phenotype. To determine a role of AKR1B1 in the degenerative phenotype, transgenic and non-transgenic control litters were treated with sorbinil, an aldose reductase inhibitior (ARI). Sorbinil was provided to the mother and pups from P1 in the drinking water and lenses evaluated at P14 and 5 weeks.

Results: : AKR1B1 transgenic mice with the highest levels of protein expression (PAR37 and PAR39) display a lens degenerative phenotype while the strain with much lower expression (PAR40) exhibits normal lens morphology. The degenerative phenotype involves lens opacity, the abnormal localization of nucleated cells both beneath the anterior epithelium as well as near the posterior pole and the presence of large vacuoles primarily in the lens bow region. Aberrant nucleated cells were present both singularly among the cortical fibers and in plaques extending from the anterior epithelium. The plaques are densely packed and positively stain for α-smooth muscle actin, a marker for epithelial-to-mesenchymal transition (EMT). The phenotype was suppressed through treatment with sorbinil. Treated high expressing transgenic mice showed reduced lens opacity and exhibited normal nuclear localization while only vacuoles in the lens bow region remained.

Conclusions: : Elevated levels of AKR1B1 expression may have consequences not only through metabolic product accumulation but also through effects on lens cell differentiation, localization and cell cycle kinetics.

Keywords: enzymes/enzyme inhibitors • EMT (epithelial mesenchymal transition) • cataract 
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