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Koji M Nishiguchi, Kosuke Fujita, Yukihiro Shiga, Toru Nakazawa; The effect of timing on visual restoration of Gnat1/Pde6c double-knockout mouse through AAV-mediated gene supplementation. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4479.
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© ARVO (1962-2015); The Authors (2016-present)
To determine the differential effect of treatment timing on visual restoration using mice defective of both rod and cone function.
Mice severely defective of both rod and cone function from birth was generated through cross-breeding (Gnat1/Pde6c double-knockout mice). The mice were supplemented with Gnat1 using AAV2/8 at 3W, 3M, and 9M. Histology was examined with immunohistochemistry and visual function was assessed by measuring visually evoked potentials (VEPs) and opto-kinetic responses (visual acuity and contrast sensitivity) 2 weeks after the treatment. The data was compared between the treatment groups.
The double KO mice were confirmed to be blind as measured by opto-kinetic responses, while the mice retained weak light perception as measured by VEP. Progressive decline in PNA-positive cones were noted with increasing age while the number of cells in the outer nuclear layer, mostly representing rods, remained essentially unchanged. Visual function as probed by VEPs and visual acuity did not differ between the treatment groups treated at 3W, 3M, and 9 M. Meanwhile, a modest decline in contrast sensitivity was detected only in mice treated at 9M (58.8 ± 2.5%) compared to 1M (50.6 ± 4.9%) and 3M (45.8 ± 2.9%).
The timing of visual restoration had only a modest impact on the visual function in blind mice. The visual cortex have the capacity to accomodate and process novel visual inputs mediated by the gain of retinal function that takes place well beyond adulthood in mice.
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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