July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Enhanced temporal contrast sensitivity precedes retinal degeneration in a P23H mouse model of retinitis pigmentosa
Author Affiliations & Notes
  • Rose Lynn Pasquale
    Ophthalmology, Center for Vision Research, SUNY Upstate Medical University, Syracuse, New York, United States
    Neuroscience, SUNY Upstate Medical University, Syracuse, New York, United States
  • Michael Booth
    SUNY Upstate Medical University, New York, United States
  • Barry Knox
    Ophthalmology, Center for Vision Research, SUNY Upstate Medical University, Syracuse, New York, United States
  • Yumiko Umino
    Ophthalmology, Center for Vision Research, SUNY Upstate Medical University, Syracuse, New York, United States
  • Eduardo C Solessio
    Ophthalmology, Center for Vision Research, SUNY Upstate Medical University, Syracuse, New York, United States
  • Footnotes
    Commercial Relationships   Rose Pasquale, None; Michael Booth, None; Barry Knox, None; Yumiko Umino, None; Eduardo Solessio, None
  • Footnotes
    Support  NEI R01: EY026216
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 3117. doi:
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      Rose Lynn Pasquale, Michael Booth, Barry Knox, Yumiko Umino, Eduardo C Solessio; Enhanced temporal contrast sensitivity precedes retinal degeneration in a P23H mouse model of retinitis pigmentosa. Invest. Ophthalmol. Vis. Sci. 2019;60(9):3117.

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

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Abstract

Purpose : Retinitis pigmentosa (RP) is a slow progressing disease that often goes unnoticed until degeneration is advanced. A common subtype of RP is associated with a P23H mutation in rhodopsin, which is characterized by fast rod inactivation kinetics compared to controls in both mouse models and human patients. We have previously shown that fast rod inactivation kinetics result in enhanced retinal and visual temporal contrast sensitivity (TCS) in mouse. We hypothesized that mice heterozygote for the P23H mutation (RhoP23H/+) would also exhibit enhanced TCS.

Methods : We used flicker electroretinograms (ERGs) to determine retinal TCS and the optomotor behavior assay to determine behavioral TCS in control and RhoP23H/+ mice (P30-P120) under mesopic conditions (~1000 R*/rod/s). To assess cone contributions, RhoP23H/+ mice were bred with GNAT2cpfl3 mice (desensitized cones). To control for the reduction in rhodopsin levels in the rods of RhoP23H/+mice, we measured TCS in Rho+/- mice. We used OCT and flash ERGs to assess the extent of retinal degeneration. Statistical analysis: 2-Way RM ANOVA, n ≥ 5 mice.

Results : At early stages of retinal degeneration (P30-P60), retinal and optomotor TCS of RhoP23H/+mice was enhanced 1.5-2.5 fold compared to controls in response to flicker frequencies of 1.5-12 Hz (p<0.01). As degeneration progressed (P90), retinal TCS of RhoP23H/+mice decreased in response to low frequencies, limiting the range of enhanced TCS to 6-12 Hz (p<0.05). At later stages of degeneration (P120), RhoP23H/+mice displayed equivalent retinal TCS compared to controls at all temporal frequencies (p>0.05). TCS of Rho+/- mice was also enhanced 1.5-2.5 fold compared to controls at all ages, prior to the manifestation of retinal degeneration (P30-P120, p<0.05). Control ERG recordings indicate that the paradoxical enhancement in retinal TCS: (1) cannot be fully explained in terms of unequal activation of rhodopsin in degenerating retinas and (2) is not mediated by cones or altered rod-cone interactions. This suggests that an alternative mechanism(s) such as the kinetics of the photoresponse, underlies the increase in retinal and optomotor TCS.

Conclusions : Our results suggest that behavioral enhancement of TCS could be a non-invasive, early diagnostic tool for RhoP23H/+ and other forms of RP that present with fast rod kinetics and/or reduced rhodopsin expression.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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