August 2009
Volume 9, Issue 8
Free
Vision Sciences Society Annual Meeting Abstract  |   August 2009
Cortical recovery following gene therapy in a canine model of achromatopsia
Author Affiliations
  • Guy Gingras
    Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA
  • Andras M. Komaromy
    Clinical Studies, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA
  • Ben Tseng
    Thomas Jefferson University Medical College, Philadelphia, PA
  • John J. Alexander
    Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL
  • Vince V. Chiodo
    Ophthalmology, University of Florida College of Medicine, Gainesville, FL
  • William W. Hauswirth
    Ophthalmology, University of Florida College of Medicine, Gainesville, FL, and Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, FL
  • Gregory M. Acland
    Baker Institute for Animal Health, Cornell University College of Veterinary Medicine, Ithaca, NY
  • Gustavo D. Aguirre
    Clinical Studies, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA
  • David H. Brainard
    Psychology, University of Pennsylvania, Philadelphia, PA
  • Geoffrey K. Aguirre
    Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA
Journal of Vision August 2009, Vol.9, 311. doi:10.1167/9.8.311
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      Guy Gingras, Andras M. Komaromy, Ben Tseng, John J. Alexander, Vince V. Chiodo, William W. Hauswirth, Gregory M. Acland, Gustavo D. Aguirre, David H. Brainard, Geoffrey K. Aguirre; Cortical recovery following gene therapy in a canine model of achromatopsia. Journal of Vision 2009;9(8):311. doi: 10.1167/9.8.311.

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

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Abstract

Purpose: To measure the cortical response to visual stimulation in dogs with hereditary loss of retinal cone function using rod- and cone-directed stimuli.

Methods: Two normal dogs (CNGB3 null mutant carriers), 5 achromatopsia-affected dogs (CNGB3 mutants with S- and L/M-cone dysfunctions), and 2 CNGB3 mutants treated at 1.5 and 3 months of age (recovered L/M-cone function demonstrated by ERG) were studied using BOLD fMRI. Prior to the imaging studies, the treated animals received unilateral recombinant adeno-associated virus (rAVV) subretinal injections containing human CNGB3 cDNA. During scanning, the animals were sedated with Ketamine/Valium and mechanically ventilated following neuromuscular blockade. Rod- and cone-directed stimuli were developed using the silent-substitution method, determined with respect to published spectral sensitivity properties of the canine L/M-cone and rod opsins. Visual stimulation was a 4-quadrant checkerboard, 5 Hz flicker presented for 30 seconds, alternating with a static gray screen. Scanning was conducted with low (0.41 cd/m2) and high (1194 cd/m2) average luminance stimuli, corresponding to the canine scotopic and photopic range.

Results: Following transformations of functional data to a standardized canine digital atlas, activation was observed in the lateral gyrus (striate/parastriate cortex). Within this region, the response to high luminance, cone-directed stimuli in the normal and treated animals was more than double that of the affected CNGB3 mutants (140 mm3 vs. 310 mm3, p=0.068). No population differences were observed for the rod-directed responses or at low luminance.

Conclusions: These results suggest that rod- and cone-directed cortical responses can be identified and studied in a canine model of achromatopsia. More importantly, the visual recovery that can be measured in affected animals following gene therapy suggests restoration of L/M-cone cortical responses.

Gingras, G. Komaromy, A. M. Tseng, B. Alexander, J. J. Chiodo, V. V. Hauswirth, W. W. Acland, G. M. Aguirre, G. D. Brainard, D. H. Aguirre, G. K. (2009). Cortical recovery following gene therapy in a canine model of achromatopsia [Abstract]. Journal of Vision, 9(8):311, 311a, http://journalofvision.org/9/8/311/, doi:10.1167/9.8.311. [CrossRef]
Footnotes
 NIH (EY06855, EY08571, EY10016, EY11123, EY13729, EY17549, K12 EY15398, NS36302, P30 EY01583, T32 DK07518), Burroughs-Wellcome Fund, Foundation Fighting Blindness, Hope for Vision, Juvenile Diabetes Research Foundation, Macular Vision Research Foundation, ONCE International Prize for R&D in Biomedicine and New Technologies for the Blind, Research to Prevent Blindness, Inc.
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