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E. Lheriteau, L. Libeau, A. Mendes-Madeira, J.-Y. Deschamps, M. Weber, D. Nivard, N. Provost, Y. Cherel, P. Moullier, F. Rolling; Characterization of the Retinal Degeneration Affecting the Miniature Longhaired Dachshunds Carrying a Mutation in the Rpgrip Gene. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3068.
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To characterise the pathological and the electrophysiological features of a retinal degeneration in miniature longhaired dachsund (MLHD) dogs carrying a mutation in the RPGRIP gene, in order to define the optimal therapeutic window for retinal gene therapy.
Four RPGRIP-/- MLHD dogs from our dog colony have been observed for 2 years by a variety of non invasive examinations : bilateral full-field electroretinograms (ERG) to evaluate retinal function, fundus photographs to evaluate retinal vascularization, lens photographs to evaluate crystalline lens opacity, and optical coherence tomographs (OCT) to evaluate retinal thickness. Hematoxylin and eosin stain as well as in situ end labeling of DNA terminal dUTP nick end labeling (TUNEL) were also performed on retinal sections.
The ERG of 2-months-old affected MLHD shows that the flicker cone specific ERG is severely reduced in amplitude while the rod specific ERG is still normal at this stage. At 9 months of age, both cone and rod functions were severely reduced. Fundus photographs of RPGRIP-/- dogs show that blood vessels diameter reduce dramatically over the first year of life and that crystalline lens opacification start at the age of 21 months. OCT and histological study reveal that the retinal thickness decrease in a statistically significant manner over a 6 months period. Moreover, TUNEL-positive cells were detected on retinal sections at 2 and 11 months of age.
The fact that there are close similarities between the clinical characteristics diseases resulting from RPGRIP gene mutations in humans and in the dog make this RPGRIP-/- MHLD a valuable model for the evaluation of gene replacement therapy. Because of the early onset and the rapid evolution of the retinal degeneration, gene therapy treatment in these canine model of Leber congenital amaurosis will have to be performed as early as possible.
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