May 2005
Volume 46, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2005
Functional Analysis of Mouse Mutants With Impairment of Systemic Retinoid and Carotinoid Pathways
Author Affiliations & Notes
  • E. Fahl
    Retinal Electrodiagnostic Research Group, University Eye Hospital II, Tuebingen, Germany
  • D. Nohr
    Institute of Biological Chemistry and Nutritional Science, University Hohenheim, Stuttgart, Germany
  • K. Hudl
    Retinal Electrodiagnostic Research Group, University Eye Hospital II, Tuebingen, Germany
  • E. Zrenner
    Retinal Electrodiagnostic Research Group, University Eye Hospital II, Tuebingen, Germany
  • J. von Lintig
    Institute of Biology I (Neurobiology and Animal Physiology), University Freiburg, Freiburg, Germany
  • N. Ghyselinck
    Physiological Genetics, IGBMC, Illkirch Cedex, France
  • R. Goralczyk
    DSM Nutritional Products Ltd., R&D Human Nutrition and Health, Basel, Switzerland
  • A. Wyss
    DSM Nutritional Products Ltd., R&D Human Nutrition and Health, Basel, Switzerland
  • M. Seeliger
    Retinal Electrodiagnostic Research Group, University Eye Hospital II, Tuebingen, Germany
  • Footnotes
    Commercial Relationships  E. Fahl, DSM Nutritional Products Ltd. F; D. Nohr, None; K. Hudl, DSM Nutritional Products Ltd. F; E. Zrenner, None; J. von Lintig, None; N. Ghyselinck, None; R. Goralczyk, DSM Nutritional Products Ltd. E; A. Wyss, DSM Nutritional Products Ltd. E; M. Seeliger, None.
  • Footnotes
    Support  DFG Se 837/3–1, Netzwerk Molekulare Ernährungsforschung, DSM, Pro Retina
Investigative Ophthalmology & Visual Science May 2005, Vol.46, 1751. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      E. Fahl, D. Nohr, K. Hudl, E. Zrenner, J. von Lintig, N. Ghyselinck, R. Goralczyk, A. Wyss, M. Seeliger; Functional Analysis of Mouse Mutants With Impairment of Systemic Retinoid and Carotinoid Pathways . Invest. Ophthalmol. Vis. Sci. 2005;46(13):1751.

      Download citation file:


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

      ×
  • Supplements
Abstract

Abstract: : Purpose: To investigate the impact of retinol and ß–carotene deficiency on retinal function in mice. Methods: Retinol deficiency is present in retinol binding protein knockout mice (RBP–/–), whereas ß–carotene 15,15’–monooxygenase knockout mice (BCMO1–/–) mimic ß–carotene deficiency at least partially due to reduced cleavage. RBP–/– and BCMO1–/– mice were studied by means of electroretinography (ERG). RBP–/– mice and control animals were kept on a vitamin A–free diet for 11 weeks prior to examination. BCMO1–/– mice and their respective controls were split in two groups, one kept on 200 IU/kg vitamin A, the other receiving additionally 1000 ppm ß–carotene supplementation for 3 months. Amplitudes and implicit times of the ERG responses were calculated. Retina and eye cup retinoid and carotenoid contents were investigated via HPLC. The study was performed in accordance with the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research. Results: RBP–/– mice showed a reduction of retinal sensitivity of the rod system by about 1.2–1.4 log units, imposing as a right shift of the amplitude peak in the 6 Hz flicker, and of the implicit time curve in scotopic single flash ERG. In BCMO1–/– mice, only a moderate effect on retinal sensitivity was found. Apparently, the control group fed with additional ß–carotene was able to metabolize it –in contrast to the respective BCMO1 group–, leading to a higher sensitivity of about 0.4 log units in comparison to that and the two unsupplemented groups. These results were supported by biochemical measurements of retina and eye cup preparations. Conclusions: The lack of retinol supply to retina and RPE in RBP deficient mice had a strong effect on retinal function, and was comparable to the situation in human patients (Seeliger, IOVS 1999). In a situation of reduced retinol availability (induced in all groups of the BCMO1 study), retinol levels were enhanced by cleavage of ß–carotene, as shown by the improved performance of the supplemented controls in comparison with the BCMO1 knockouts. ß–carotene may thus play a role as alternative tissue source of retinol in RBP deficiency, explaining the subtotal loss in affected patients and mice.

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

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×