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Gobinda Pangeni, James W Fransen, Ian Scott Pyle, Maureen A McCall, ; Slow Onset and Protracted Decline in Visual Function in the P23H Rhodopsin Knockin Mouse Model of Retinitis Pigmentosa. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4260.
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© ARVO (1962-2015); The Authors (2016-present)
The P23H rhodopsin mutation causes retinitis pigmentosa (RP) leading to a loss of rod photoreceptors and compromised scotopic vision. The superior colliculus (SC) is a major target of retinal ganglion cells (RGCs) and changes in RGC and SC activity in other rodent models of RP have been noted. We used a P23H rhodopsin knockin mouse to record visual responses in RGCs and SC and characterized changes that occur during the prolonged degenerative process.
Light evoked responses were recorded in RGCs and in the SC of C57BL/6J (WT) and P23H homozygous and heterozygous knockin (P23HKI-/- and KI+/-) mice from postnatal day (P) 30 until P300. RGC responses were recorded on a multi-electrode array and SC responses were recorded in vivo, using tungsten electrodes. The same photopic background and the full-field flash stimuli were used in both preparations.
Similar to other RP rodent models, visually responsive RGCs decline with age and responses declined more rapidly in P23HKI-/- than P23H KI+/- littermates. At P50, 20% of P23HKI-/- RGCs were visually responsive compared to 100% in P23H KI+/- RGCs. At P90, 2% of P23HKI-/- RGCs were visually responsive, whereas 8% of P23H KI+/- RGCs remained visually responsive at P300. This protracted decline in visual function allowed us to characterize the degenerative changes as it began in a mature retina and progressed slowly, similar to human RP. We observed changes not previously noted in other rodent RP models. At P90 in many P23H KI+/- RGCs, light evokes only a maintained suppression in spontaneous activity matched to stimulus duration. Peak firing rates of visually responsive P23H KI+/- RGCs were lower than WT at P300 and both On and Off RGC were similarly affected. At P300, there were equal On and Off RGCs. There was no hyperactivity in P23H KI+/- RGCs compared to WT, regardless of age. Only visually non-responsive P23H KI+/- RGCs had a ~4Hz rhythmic component in their spontaneous activity. We found similar changes in P23H KI+/- SC.
Degeneration in the P23H mouse begins after the retina is mature and visual function declines gradually through one year. This slow decline in P23H KI+/- mice allows a better characterization of potential changes in human patients with RP. We find that decline in visual function in the retina and SC is similar.
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