June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Variable cone dysfunction and progressive ophthalmoscopic changes in a canine model of RPGRIP1 and MAP9 multigenic cone-rod dystrophy
Author Affiliations & Notes
  • Keiko Miyadera
    Clinical Studies - Philadelphia, University of Pennsylvania, School of Veterinary Medicine, Philadelphia, Pennsylvania, United States
  • Felipe Pompeo Marinho
    RDSF, University of Pennsylvania, School of Veterinary Medicine, Kennett Square, Pennsylvania, United States
  • Kendra McDaid
    RDSF, University of Pennsylvania, School of Veterinary Medicine, Kennett Square, Pennsylvania, United States
  • Valerie Liliane Dufour
    RDSF, University of Pennsylvania, School of Veterinary Medicine, Kennett Square, Pennsylvania, United States
  • Simone Iwabe
    Clinical Studies - Philadelphia, University of Pennsylvania, School of Veterinary Medicine, Philadelphia, Pennsylvania, United States
  • Gautami Das
    Clinical Studies - Philadelphia, University of Pennsylvania, School of Veterinary Medicine, Philadelphia, Pennsylvania, United States
  • Gustavo D Aguirre
    Clinical Studies - Philadelphia, University of Pennsylvania, School of Veterinary Medicine, Philadelphia, Pennsylvania, United States
  • Footnotes
    Commercial Relationships   Keiko Miyadera, None; Felipe Marinho, None; Kendra McDaid, None; Valerie Dufour, None; Simone Iwabe, None; Gautami Das, None; Gustavo Aguirre, None
  • Footnotes
    Support  NIH Grant EY06855 and EY017549; Foundation Fighting Blindness; URF-UPenn; Van Sloan Foundation
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 269. doi:
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      Keiko Miyadera, Felipe Pompeo Marinho, Kendra McDaid, Valerie Liliane Dufour, Simone Iwabe, Gautami Das, Gustavo D Aguirre; Variable cone dysfunction and progressive ophthalmoscopic changes in a canine model of RPGRIP1 and MAP9 multigenic cone-rod dystrophy. Invest. Ophthalmol. Vis. Sci. 2017;58(8):269.

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

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Abstract

Purpose : A canine multigenic model of cone-rod dystrophy (cord1) has been associated with mutations in RPGRIP1 and MAP9, but prediction of the disease course has remained challenging. None of the RPGRIP1ins/ins animals in the current research colony has developed clinical blindness, but some show defective cone ERG response. To understand the phenotypic spectrum of cord1, we studied in vivo retinal function and structure in genotype-ascertained animals.

Methods : Sixty-four dogs from a purpose-bred research colony, genotyped for the known RPGRIP1 and MAP9 mutations, underwent periodic ophthalmic examinations and full-field ERGs. Visually-guided behavior was tested using an obstacle course under different illuminations. To assess individual L/M- and S-cone functions, light-adapted chromatic ERGs were done using color flashes of increasing intensity on different color background light. Fundus was imaged in vivo using confocal scanning laser ophthalmoscope/spectral-domain optical coherence tomography (OCT).

Results : Cone-derived ERG responses ranged from absent, reduced, to normal across RPGRIP1ins/ins animals of all MAP9 genotypes. Both L/M- and S-cones were equally affected in the animals tested, and rod-derived ERGs were normal in all animals. Visually-guided behavior in RPGRIP1ins/insMAP9+/del littermates that showed normal- or absent-cone ERG function revealed comparable performance at all light conditions. These functional phenotypes remained stable for up to 5 years. The RPGRIP1ins/ins progeny in the current colony showed normal retinas in the early years of life, but, with age, some developed coalescing dark discoloration that extended from the periphery. As well, OCT was normal in younger animals, but progressive ONL thinning was observed among some older absent-cone ERG mutants. Significant variation in ophthalmoscopic and OCT imaging was observed and the double homozygotes tended to show earlier onset and faster progression.

Conclusions : RPGRIP1ins/ins animals show a broad clinical spectrum independent of the MAP9 status. While the two homozygous gene mutations have been associated with cord1, neither mutation by itself leads to any specific phenotype, and involvement of other genetic factors are indicated.

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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