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Kris Walker, Andras M Komaromy, Gustavo D Aguirre, Geoffrey K Aguirre; Staged gene therapy of canine retinal blindness does not produce cortical amblyopia for the later treated eye. Journal of Vision 2012;12(9):1360. doi: 10.1167/12.9.1360.
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© ARVO (1962-2015); The Authors (2016-present)
Dark rearing of animals extends the window of ocular dominance cortical plasticity into adulthood, as demonstrated by the induction of amblyopia in an eye given brief monocular deprivation following reversal of dark rearing. In contrast to dark-rearing, binocular lid-suture does not produce this effect (GD Mower, Brain Res 1981). Is the visual deprivation of inherited retinal disease (specifically, RPE65-LCA) akin to dark-rearing or lid suture? This is clinically relevant as planned gene-therapy for this disorder is delivered by staged, monocular treatments, raising the possibility of therapy-induced amblyopia in the later treated eye. We studied four dogs with congenital blindness from RPE65 mutations. Two of the dogs ("staged") had one eye treated at 220 days of age. The second eye, and both eyes of the "simultaneous" dogs, were treated at day 320. MION fMRI during isoflurane anesthesia and monocular visual stimulation (5 Hz full-field luminance flicker) was collected at day 360, and again at day 420. Rod-cone b-wave amplitudes from ERG were also obtained. We tested for reduced amplitude of cortical response to the later treated eye in canine V1. Retinal gene-therapy produced roughly equal recovery of ERG responses in all animals, with the exception of a smaller response in the later treated eye of one staged animal. Gene-therapy for all 8 eyes restored cortical V1 responses to roughly half the amplitude seen in normal control animals. No reduction in amplitude to the later treated eye was observed. Variations in ERG responses did not account for any of the small variation in cortical responses seen. In conclusion, we did not observe evidence of treatment-induced amblyopia in the amplitude of cortical response, arguing against the equivalence of the visual deprivation from dark-rearing and RPE65-LCA blindness.
Meeting abstract presented at VSS 2012
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