July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
The ocular manifestations of Fanconi anemia in a genetic mouse model
Author Affiliations & Notes
  • Sandrine Joly
    Ophthalmology, Centre de recherche du CHUQ/University Laval, Quebec, Quebec, Canada
  • Léa Rodriguez
    Ophthalmology, Centre de recherche du CHUQ/University Laval, Quebec, Quebec, Canada
  • Julius Baya Mdzomba
    Ophthalmology, Centre de recherche du CHUQ/University Laval, Quebec, Quebec, Canada
  • Madeleine Carreau
    Pediatry, Centre de recherche du CHUQ/University Laval, Quebec, Quebec, Canada
  • Vincent Pernet
    Ophthalmology, Centre de recherche du CHUQ/University Laval, Quebec, Quebec, Canada
  • Footnotes
    Commercial Relationships   Sandrine Joly, None; Léa Rodriguez, None; Julius Mdzomba, None; Madeleine Carreau, None; Vincent Pernet, None
  • Footnotes
    Support  FRQS, grant #30633; CFI, project #34204; NSERC, grant #RGPIN-2015-05084
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 4738. doi:
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      Sandrine Joly, Léa Rodriguez, Julius Baya Mdzomba, Madeleine Carreau, Vincent Pernet; The ocular manifestations of Fanconi anemia in a genetic mouse model. Invest. Ophthalmol. Vis. Sci. 2019;60(9):4738.

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

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Abstract

Purpose : Fanconi anemia (FA) is a rare genetic disorder mainly associated with bone marrow failure and a propensity to tumor formation. However, frequent ocular manifestations have been reported in patients with FA. They include micro-ophthalmia, ptosis, and reduced optic disc. FA gene products like the FancC protein are critical in major cell events including cell division, DNA repair and autophagy. The aim of this study was to determine whether FancC-/- mice could be used as a model to study developmental ocular impairments found in FA.

Methods : In adult FancC-/-, FancC+/- and Wild-type (WT) C57BL/6J mice, retinal function changes were monitored by electroretinogram (ERG) recordings at ~80-90 days of life. The histological development of retinal cell layers was studied by immunofluorescence. To this purpose, specific cell markers were used to visualize neuronal subpopulations: RNA-binding protein with multiple splicing (RBPMS) for retinal ganglion cells (RGCs), Choline acetyltransferase (ChAT) for starburst amacrine cells, PKCα for rod bipolar cells, Tyrosine hydroxylase (TH) for dopaminergic amacrine cells and recoverin for photoreceptors.

Results : All FancC-/- mice presented external ocular anomalies such as apparent bilateral anophthalmia (3 mice), apparent unilateral anophthalmia (8 mice), unilateral micro-ophthalmia (8 mice) compared with WT (20 mice) and heterozygous animals (22 mice) that appeared normal. ERG recordings in visibly normal FancC-/- eyes did not show significant a-wave and b-wave amplitude reduction compared to other genotypes, suggesting that FancC is dispensable for the retinal function. Nevertheless, ERG measurements showed more variability between animals within the FancC-/- group than WT and FancC+/- littermates. Apparent anophthalmia turned out to be severe micro-ophthalmia, whose vestigial eyes were removed from the depth of the orbit and examined histologically. Their atrophied retinae contained folded and irregular cell layers composed of RBPMS-positive RGCs, ChAT-labelled starburst amacrine cells, PKCα-stained bipolar cells and recoverin-positive photoreceptors. In normally formed FancC-/- eyes, the dorsoventral length of the retina, and the number of RGCs and amacrine cells did not differ from those of the two other groups.

Conclusions : Our data suggest that FancC-/- mice are a good model to study developmental ocular impairments associated with FA.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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