May 2007
Volume 48, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2007
Functional Consequences of Retinoid Depletion in Mice
Author Affiliations & Notes
  • E. Fahl
    Retinal Diagnostics Research Group, University Eye Hospital II, Tuebingen, Germany
  • N. Tanimoto
    Retinal Diagnostics Research Group, University Eye Hospital II, Tuebingen, Germany
  • S. C. Beck
    Retinal Diagnostics Research Group, University Eye Hospital II, Tuebingen, Germany
  • V. Oberhauser
    Institute of Biology I, University of Freiburg, Freiburg, Germany
  • S. Hessel
    Institute of Biology I, University of Freiburg, Freiburg, Germany
  • N. B. Ghyselinck
    Physiological Genetics, IGBMC, Illkirch Cedex, France
  • A. Wyss
    DSM Nutritional Products Ltd., R & D Human Nutrition and Health, Basel, Switzerland
  • J. von Lintig
    Institute of Biology I, University of Freiburg, Freiburg, Germany
  • M. W. Seeliger
    Retinal Diagnostics Research Group, University Eye Hospital II, Tuebingen, Germany
  • Footnotes
    Commercial Relationships E. Fahl, None; N. Tanimoto, None; S.C. Beck, None; V. Oberhauser, None; S. Hessel, None; N.B. Ghyselinck, None; A. Wyss, DSM Nutritional Products Ltd., E; J. von Lintig, None; M.W. Seeliger, None.
  • Footnotes
    Support Ministry of Science, Research and the Arts, Baden-Wuerttemberg, Germany (NeME), DFG Se837/3-1
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 2996. doi:
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      E. Fahl, N. Tanimoto, S. C. Beck, V. Oberhauser, S. Hessel, N. B. Ghyselinck, A. Wyss, J. von Lintig, M. W. Seeliger; Functional Consequences of Retinoid Depletion in Mice. Invest. Ophthalmol. Vis. Sci. 2007;48(13):2996.

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

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Abstract

Purpose:: To investigate the functional impact of retinoid depletion in RBP4-/-BCMO1-/- double knock-out mice.

Methods:: RBP4-/-BCMO1-/- double knock-out mice were generated by crossing retinol binding protein knock-out mice (RBP4-/-) representing systemic retinol deficiency and ß-carotene 15,15’-monooxygenase knock-out mice (BCMO1-/-) lacking the ß-carotene cleavage enzyme. Retinal function of dark-adapted mice aged 3 months was analyzed with both scotopic and photopic single flash and flicker electroretinography (ERG). Morphology was examined in vivo with scanning-laser-ophthalmology (SLO). Whole eye retinoid content was determined by HPLC. The study was performed in accordance with the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research.

Results:: RBP4-/-BCMO1-/- double knock-out mice showed a much stronger reduction in ocular retinoid levels than the RBP4-/- knock-out mice. HPLC analysis of the whole eye extracts revealed no detectable retinyl esters and only trace amounts of 11-cis-retinal. Functionally, these mice showed a pathological right shift both in the VlogI function of scotopic single flash recordings and the amplitude peak of the 6Hz flicker ERG. In SLO imaging, severe morphological changes, including persistent vitreal vessels and colobomas, were observed.

Conclusions:: The lack of both the retinol-binding-protein and the ß-carotene cleavage enzyme in RBP4-/-BCMO1-/- double knock-out mice led to a severe retinoid-deficiency of the eyes that caused severe functional and structural alterations.

Keywords: vitamin A deficiency • retinoids/retinoid binding proteins • electroretinography: non-clinical 
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