June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
Photoreceptor Vision and Structure in LCA1 caused by Mutations in GUCY2D
Author Affiliations & Notes
  • Artur Cideciyan
    Dept of Ophthalmology, Scheie Eye Institute, Univ of Pennsylvania, Philadelphia, PA
  • Samuel Jacobson
    Dept of Ophthalmology, Scheie Eye Institute, Univ of Pennsylvania, Philadelphia, PA
  • Igor Peshenko
    Pennsylvania College of Optometry, Salus University, Elkins Park, PA
  • Alexander Sumaroka
    Dept of Ophthalmology, Scheie Eye Institute, Univ of Pennsylvania, Philadelphia, PA
  • Elena Olshevskaya
    Pennsylvania College of Optometry, Salus University, Elkins Park, PA
  • Alejandro Roman
    Dept of Ophthalmology, Scheie Eye Institute, Univ of Pennsylvania, Philadelphia, PA
  • Sam Sadigh
    Dept of Ophthalmology, Scheie Eye Institute, Univ of Pennsylvania, Philadelphia, PA
  • Elise Heon
    Dept of Ophthalmology and Vision Sciences, University of Toronto, Toronto, ON, Canada
  • Edwin Stone
    Dept of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, IA
  • Alexander Dizhoor
    Pennsylvania College of Optometry, Salus University, Elkins Park, PA
  • Footnotes
    Commercial Relationships Artur Cideciyan, None; Samuel Jacobson, None; Igor Peshenko, None; Alexander Sumaroka, None; Elena Olshevskaya, None; Alejandro Roman, None; Sam Sadigh, None; Elise Heon, None; Edwin Stone, None; Alexander Dizhoor, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 654. doi:
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      Artur Cideciyan, Samuel Jacobson, Igor Peshenko, Alexander Sumaroka, Elena Olshevskaya, Alejandro Roman, Sam Sadigh, Elise Heon, Edwin Stone, Alexander Dizhoor; Photoreceptor Vision and Structure in LCA1 caused by Mutations in GUCY2D. Invest. Ophthalmol. Vis. Sci. 2013;54(15):654.

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

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Abstract

Purpose: : The GUCY2D gene encodes retinal membrane guanylyl cyclase (RetGC1), a key component of the phototransduction machinery in photoreceptors. Mutations in GUCY2D cause Leber congenital amaurosis type 1 (LCA1), an autosomal recessive human retinal blinding disease. The effects of RetGC1 deficiency on human rod and cone photoreceptor structure and function are currently unknown.

Methods: We characterized a cohort of patients (ages 6 mos - 37 yrs) with GUCY2D mutations using spectral-domain OCT, full-field electroretinogram (ERG), full-field stimulus testing (FST), dark- and light-adapted chromatic static threshold perimetry, and direct transient pupillary light reflex (TPLR). Adaptation of rod- and cone-mediated vision to increasing levels of background lights was quantified with FST. A mobility performance task was used to quantify the ability of the patients to move through an indoor obstacle course under different ambient illuminations.

Results: Analyses of retinal architecture by SD-OCT indicated intact rod photoreceptors in all patients; foveal cones showed abnormalities. By functional phenotype, there were patients with and without detectable cone vision. Rod vision could be unexpectedly retained but the extent of rod vision did not correlate with that of cone vision or age. In patients without detectable cone vision, rod vision continued to function unsaturated under bright ambient illumination. The differences in cone function, but not rod function, were explained by the in vitro biochemical activity of the mutants.

Conclusions: We postulate a relationship between the level of RetGC1 activity and the degree of cone vision, and argue for cone function being the efficacy outcome measure in clinical trials of gene augmentation therapy in LCA1.

Keywords: 696 retinal degenerations: hereditary • 550 imaging/image analysis: clinical • 641 perception  
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