June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
The retinal phenotype of an animal model of the HANAC syndrome
Author Affiliations & Notes
  • Alix Trouillet
    Institut de la Vision, INSERM/CNRS/UPMC/CHNO des XV-XX, Paris, France
  • Emmanuelle Plaisier
    APHP-Hôpital Tenon, Paris, France
  • Henri Lorach
    Institut de la Vision, INSERM/CNRS/UPMC/CHNO des XV-XX, Paris, France
  • Julie Dégardin
    Institut de la Vision, INSERM/CNRS/UPMC/CHNO des XV-XX, Paris, France
  • Manuel Simonutti
    Institut de la Vision, INSERM/CNRS/UPMC/CHNO des XV-XX, Paris, France
  • Michel Paques
    Institut de la Vision, INSERM/CNRS/UPMC/CHNO des XV-XX, Paris, France
  • Jose Sahel
    Institut de la Vision, INSERM/CNRS/UPMC/CHNO des XV-XX, Paris, France
  • Pierre Ronco
    APHP-Hôpital Tenon, Paris, France
  • Serge Picaud
    Institut de la Vision, INSERM/CNRS/UPMC/CHNO des XV-XX, Paris, France
  • Footnotes
    Commercial Relationships Alix Trouillet, None; Emmanuelle Plaisier, None; Henri Lorach, None; Julie Dégardin, None; Manuel Simonutti, None; Michel Paques, MerckSerono (C), Roche (C), Sanofi (C); Jose Sahel, UPMC/Essilor (P), Second Sight (F); Pierre Ronco, None; Serge Picaud, UPMC (P), Pixium Vision (C)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 5094. doi:https://doi.org/
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      Alix Trouillet, Emmanuelle Plaisier, Henri Lorach, Julie Dégardin, Manuel Simonutti, Michel Paques, Jose Sahel, Pierre Ronco, Serge Picaud; The retinal phenotype of an animal model of the HANAC syndrome. Invest. Ophthalmol. Vis. Sci. 2013;54(15):5094. doi: https://doi.org/.

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

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Abstract

Purpose: HANAC syndrome is an autosomal dominant hereditary angiopathy with nephropathy, aneurysms, and muscle cramps and occasional visual problems. People with HANAC syndrome can also experience occasional visual problems due to arterial retinal tortuosity, cataract or Axenfeld-Rieger abnormalities. It has been shown that a mutation in the gene COL4A1 is responsible for these symptoms. COL4A1 gene codes for a subtype of collagen protein mainly located in the basement membrane surrounding blood vessels. The purpose of this study was to analyze the retinal phenotype of a COL4A1 mutant mouse in order to better understand the disease physiopathology.

Methods: Homozygote and heterozygote Col4a1 deficient mice were characterized functionally by electroretinogram, and their retina was examined by ocular coherence tomography (OCT),Scanning Laser Ophthalmoscope ( SLO) and Micron III. Following the animal sacrifice, blood vessels were stained on the flat-mounted retina to reconstitute the vascular network for subsequent automated analysis by the ImageJ software. Some retinal pieces were processed for ultrastructural examination.

Results: At the functional level, the electroretinogram did show a decrease in heterozygote animals, the number of animals were too small for statistical analyses in homozygotes. Homozygote mice displayed local thinning of the retina when examined by OCT. Eye fundus examination showed depigmented areas and arteriolar tortuosity. In some animals, a breakdown of the hematoretinal barrier was indicated by fluorescein angiography. When the vascular network was quantified on retinal flatmounts, theblood vessel length was increased in transgenic animals, density of vessel branching was greater and finally, the squared curvature, an indicator of vessel tortuosity, was significantly enlarged in mutant mice. When examined at the ultrastructural level, blood vessel exhibited local thinning of the basement membrane in both heterozygote and homozygote animals.

Conclusions: This mutant mouse apparently reproduces many features of the human disease, suggesting it will provide an adequate model to investigate the retinal pathophysiology of HANAC syndrome. Further investigations will enlarged the mouse populations and will reiterate the study at different ages to further define the consequence of the blood vessel alteration. This new model could be therefore become interesting to assess potential treatments.

Keywords: 604 mutations • 636 pathobiology • 749 vascular occlusion/vascular occlusive disease  
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