May 2007
Volume 48, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2007
Distinct Visual Response Phenotypes of Rod and Cone Degenerations in Mice
Author Affiliations & Notes
  • S. Thompson
    Ophthalmology, University of Iowa, Iowa City, Iowa
    Department of Cell and Systems Biology, University of Toronto, Toronto, Ontario, Canada
  • A. R. Philp
    Ophthalmology, University of Iowa, Iowa City, Iowa
  • R. F. Mullins
    Ophthalmology, University of Iowa, Iowa City, Iowa
  • S. N. Peirson
    Nuffield Laboratory of Ophthalmology, University of Oxford, Oxford, United Kingdom
  • M. Olvera
    Ophthalmology, University of Iowa, Iowa City, Iowa
  • J. C. Janutka
    Ophthalmology, University of Iowa, Iowa City, Iowa
  • J. S. East
    Ophthalmology, University of Iowa, Iowa City, Iowa
  • E. M. Stone
    Ophthalmology, University of Iowa, Iowa City, Iowa
  • N. Mrosovsky
    Department of Cell and Systems Biology, University of Toronto, Toronto, Ontario, Canada
  • Footnotes
    Commercial Relationships S. Thompson, None; A.R. Philp, None; R.F. Mullins, None; S.N. Peirson, None; M. Olvera, None; J.C. Janutka, None; J.S. East, None; E.M. Stone, None; N. Mrosovsky, None.
  • Footnotes
    Support The Canadian Institutes of Health Research, The Howard Hughes Medical Institute, The Foundation Fighting Blindness and The Grousbeck Family Foundation
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 2494. doi:
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      S. Thompson, A. R. Philp, R. F. Mullins, S. N. Peirson, M. Olvera, J. C. Janutka, J. S. East, E. M. Stone, N. Mrosovsky; Distinct Visual Response Phenotypes of Rod and Cone Degenerations in Mice. Invest. Ophthalmol. Vis. Sci. 2007;48(13):2494.

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

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Abstract

Purpose:: Sensory light detection is the basis of formed-image and accessory visual responses such as circadian rhythm synchronization to the daily light cycle. Light acutely modifies the amount of activity in mice through two competitive processes. Negative masking is an image-independent acute suppression of activity that normally occurs in bright light. Positive masking is an increase in activity with visually guided movement, normally in dim light. These responses depend on specific combinations of photoreceptors, so that a given disorder of the retina can severely affect one visual function and leave another intact. The contribution of the photoreceptor classes to different visual functions in retinal disease was evaluated in RPE65 knockout mice (cones degenerate and rods have severely attenuated activity) and rd/rd mice (rods degenerate with an ensuing loss of cones).

Methods:: Masking was described as responses in wheel running activity during defined irradiance light pulses relative to dark baseline day measurements, and compared to wildtype responses. To suggest the basis for differences in the masking phenotype, the structural condition and functional state of the retina was evaluated by histology, quantitative PCR, and electrophysiology.

Results:: Dim light pulses did not affect the behavior of either mouse model. However, with bright light pulses we observed an enhanced negative masking response in rd/rd mice and a positive masking response in RPE65-/- mice.

Conclusions:: The absence of dim light responses in the two retinal disease models reveals an expected deficit in low light image-forming capacity. However, bright light responses were very different in the two retinal diseases. Enhanced negative masking in rd/rd mice is consistent with loss of rod dependent positive masking. However, the bright light response in RPE65-/- mice suggests that image forming capacity is retained in this model of Leber Congenital Amaurosis, although only at higher irradiances. This also points to a raised threshold for negative masking in the RPE65-/- that suggests an effect of residual rod function on the melanopsin photosensitive retinal ganglion cells. The fact that mice with different retinal diseases exhibit marked differences in masking phenotype suggests that these light responses can be valuable in monitoring and characterizing the effectiveness of novel treatment modalities.

Keywords: retina • photoreceptors: visual performance • degenerations/dystrophies 
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