September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Cholesterol homeostasis and retinal stress in anterior ischemic optic neuropathy
Author Affiliations & Notes
  • Lionel Bretillon
    CSGA, UMR6265 CNRS - 1324 INRA - University of Burgundy, Eye & Nutrition Research Group, Dijon, France
  • Cynthia Fourgeux
    CSGA, UMR6265 CNRS - 1324 INRA - University of Burgundy, Eye & Nutrition Research Group, Dijon, France
  • Jacques Bouche-Pillon
    Department of Ophthalmology, University Hospital, Dijon, France
    CSGA, UMR6265 CNRS - 1324 INRA - University of Burgundy, Eye & Nutrition Research Group, Dijon, France
  • Lucy Martine
    CSGA, UMR6265 CNRS - 1324 INRA - University of Burgundy, Eye & Nutrition Research Group, Dijon, France
  • Laurent Leclere
    CSGA, UMR6265 CNRS - 1324 INRA - University of Burgundy, Eye & Nutrition Research Group, Dijon, France
  • Niyazi Acar
    CSGA, UMR6265 CNRS - 1324 INRA - University of Burgundy, Eye & Nutrition Research Group, Dijon, France
  • Alain M Bron
    CSGA, UMR6265 CNRS - 1324 INRA - University of Burgundy, Eye & Nutrition Research Group, Dijon, France
    Department of Ophthalmology, University Hospital, Dijon, France
  • Catherine P Garcher
    CSGA, UMR6265 CNRS - 1324 INRA - University of Burgundy, Eye & Nutrition Research Group, Dijon, France
    Department of Ophthalmology, University Hospital, Dijon, France
  • Footnotes
    Commercial Relationships   Lionel Bretillon, Laboratoires HORUS PHARMA (R); Cynthia Fourgeux, None; Jacques Bouche-Pillon, None; Lucy Martine, None; Laurent Leclere, None; Niyazi Acar, Laboratoires Chauvin Bausch & Lomb (R); Alain Bron, None; Catherine Garcher, None
  • Footnotes
    Support  Regional Council of Burgundy France (PARI Agrale 1), FEDER (European Funding for Regional Economical Development),
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 109. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to Subscribers Only
      Sign In or Create an Account ×
    • Get Citation

      Lionel Bretillon, Cynthia Fourgeux, Jacques Bouche-Pillon, Lucy Martine, Laurent Leclere, Niyazi Acar, Alain M Bron, Catherine P Garcher; Cholesterol homeostasis and retinal stress in anterior ischemic optic neuropathy. Invest. Ophthalmol. Vis. Sci. 2016;57(12):109.

      Download citation file:


      © 2017 Association for Research in Vision and Ophthalmology.

      ×
  • Supplements
Abstract

Purpose : Anterior ischemic optic neuropathy (AION) is characterized by acute stress of retinal ganglion cells (RGC). Cholesterol-24S-hydroxylase (CYP46A1) is specifically expressed in RGC where it may exert neuroprotective properties by preventing from cholesterol accumulation via catalyzing the formation of 24S-hydroxycholesterol. Previous findings hypothesize the housekeeping importance of CYP46A1 in the maintenance of cholesterol in the retina. In order to better understand the role of CYP46A1 in the retina, we aimed to define whether CYP46A1 expression and 24S-hydroxycholesterol levels were modified during RGC stress in AION.

Methods : Ninety nine male Sprague Dawley rats were randomized in 2 experimental groups: AION or Optic Nerve Ischemia (ONI) (n=45 in each group), and 1 control group of animals (n=9). AION was induced in one eye of anesthetized animals by illumination of the optic nerve head using 532nm laser light (500 µm, 50mW, 12x 1-second pulses) after intravenous injection of Rose Bengal (2.5mM, 1mL/kg). The same procedure, without Rose Bengal injection, was used to induce ONI. The rats of the experimental groups were evaluated at day 3, 14, 30, 60 and 90 post-laser. Scotopic electroretinography was recorded. Glial activation was assessed by means of GFAP expression using western blot analysis, as well as CYP46A1 expression. Cytokines and chemokines were analyzed by flow cytometry in plasma and vitreous. Cholesterol and 24S-hydroxycholesterol were quantified in plasma and retina using gas chromatography.

Results : A trend towards a decrease of the electroretinographic response (a- and b-wave amplitude) was observed in AION rats at day 30. MCP-1 concentrations were significantly increased at day 3 in the vitreous of the eye submitted to AION (132±31 vs 44±13pg/mg protein, p=0.046) and plasma of AION rats (145±16 vs 93±10pg/mg protein, p=0.05), whereas no difference was found in INO groups. Despite stress induced by AION and expected loss of RGC content, CYP46A1 and 24S-hydroxycholesterol levels were maintained at a constant level.

Conclusions : Despite RGC stress triggered by AION, CYP46A1 and 24S-hydroxycholesterol were maintained at constant levels in the retina, highlighting the resilience of CYP46A1 in the retina and its crucial importance in the maintenance of cholesterol homeostasis therein.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

×
×

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.

×