June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
The Joubert Syndrome cilia proteins arl13b and ahi1 differentially modify the severity of retinal degeneration due to loss of cep290 in zebrafish
Author Affiliations & Notes
  • Ping Song
    Ophthalmic Research, Cole Eye Inst, Cleveland Clinic Fndn, Cleveland, Ohio, United States
  • Emma M Lessieur
    Ophthalmic Research, Cole Eye Inst, Cleveland Clinic Fndn, Cleveland, Ohio, United States
  • Gabrielle C Nivar
    School of Medicine, Case Western Reserve University, Cleveland, Ohio, United States
  • Brian D Perkins
    Ophthalmic Research, Cole Eye Inst, Cleveland Clinic Fndn, Cleveland, Ohio, United States
  • Footnotes
    Commercial Relationships   Ping Song, None; Emma Lessieur, None; Gabrielle Nivar, None; Brian Perkins, None
  • Footnotes
    Support  NH Grant R01 EY017037-11
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 264. doi:
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      Ping Song, Emma M Lessieur, Gabrielle C Nivar, Brian D Perkins; The Joubert Syndrome cilia proteins arl13b and ahi1 differentially modify the severity of retinal degeneration due to loss of cep290 in zebrafish. Invest. Ophthalmol. Vis. Sci. 2017;58(8):264.

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

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Abstract

Purpose : Mutations CEP290 lead to diseases ranging from non-syndromic blindness to severe, pleiotropic disorders affecting multiple organ systems degeneration. Variability in the resulting disease phenotypes, including retinal degeneration, cannot be explained by traditional genotype-phenotype correlations. The presence of genetic modifiers of CEP290 have been hypothesized to influence disease pathology. Zebrafish cep290-/- mutants undergo slow, progressive cone degeneration. The purpose of this study is to test the hypothesis that loss of cep290 sensitizes photoreceptors and heterozygous mutations in genes/proteins that functionally interact with Cep290 will accelerate degeneration.

Methods : Crosses from cep290+/-;ahi1+/- and cep290+/-;arl13+/- adults were used to generate offspring with desired phenotypes. Retinal cryosections from 5 day post fertilization (dpf) and 6-month old animals were stained peanut agglutinin (PNA) and zpr-1 to stain cone outer and inner segments, respectively, and with rhodopsin to label rod outer segments. The length and density per unit area of cone outer segments was quantified using ImageJ. Semi-thin retinal sections were examined by light microscopy.

Results : In 5 dpf larvae, rod and cone degeneration was more severe in cep290-/-;arl13b-/- mutants than cep290-/- and arl13b-/- single mutants. In 5 dpf cep290-/-;ahi1-/- mutants, cone degeneration was observed but rods were normal. At 6 months of age, cep290-/- mutants show mild thinning of the outer nuclear layer and a decrease in cones but degeneration was not accelerated in cep290-/-;arl13b+/- mutants.

Conclusions : These data suggest that Cep290 shares redundant functions with Arl13b and Ahi1 in OS biogenesis but arl13b does not function as a modifier of cep290 degeneration.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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