May 2004
Volume 45, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2004
CELL LOSS AND ERG RESPONSES IN A PIGMENTED P23H TRANSGENIC RAT MODEL OF RETINITIS PIGMENTOSA.
Author Affiliations & Notes
  • M.S. Baig–Silva
    Bioengineering, University of Illinois–Chicago, Chicago, IL
  • J.R. Hetling
    Bioengineering, University of Illinois–Chicago, Chicago, IL
  • Footnotes
    Commercial Relationships  M.S. Baig–Silva, None; J.R. Hetling, None.
  • Footnotes
    Support  The Whitaker Foundation
Investigative Ophthalmology & Visual Science May 2004, Vol.45, 5082. doi:
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      M.S. Baig–Silva, J.R. Hetling; CELL LOSS AND ERG RESPONSES IN A PIGMENTED P23H TRANSGENIC RAT MODEL OF RETINITIS PIGMENTOSA. . Invest. Ophthalmol. Vis. Sci. 2004;45(13):5082.

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

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Abstract

Abstract: : Purpose: The P23H point mutation, associated with autosomal dominant retinitis pigmentosa, was previously inserted as a transgene in albino rats, which subsequently exhibit retinal degeneration.1 As light exposure has been implicated as a factor in retinal degeneration, a pigmented P23H transgenic rat was bred. To characterize this novel animal model, changes in retinal cell counts and ERG response amplitudes were measured as a function of age. Methods: Sprague–Dawley rats homozygous for the P23H transgene (line 1, obtained from Dr. M. LaVail, UCSF) were bred with wild–type (WT) Long Evans rats to produce pigmented offspring heterozygous for the transgene. Histological changes in the retina were evaluated by thin section light microscopy. Electroretinography (ERG) was used to measure outer and inner retinal function through analysis of a– and b–wave amplitudes, respectively. Amplitude–intensity response data were fit with the function Ap = 1–exp(k Itest), where A is the amplitude at peak, k is a sensitivity parameter, and Itest is the flash strength. Results: Rod outer segment length (ROS) and the outer nuclear layer (ONL) thickness both decreased with age, being 50% reduced compared to 16 wk WT rats at approximately 16 and 14 weeks, respectively. Both a– and b–wave ERG amplitudes decrease with age, however a–wave reduction lagged b–wave reduction. Despite cell loss and decreased ERG amplitude, the sensitivity parameter, k, remained essentially constant up to 28 wks of age. Conclusions: The trends of histological and functional changes in the pigmented P23H rat retina were similar to those reported in albino P23H rats1 raised under similar light conditions. However, ONL thickness in the pigmented rat was ∼50% greater than the albino at each age investigated (4–28 wks). Amplitudes of both a– and b–waves recorded in pigmented rats were similar to those reported for albino rats at 4 wks, but significantly greater at 28 wks. 1Machida S., M. Kondo, et al. P23H rhodopsin transgenic rat: Correlation of retinal function with histopathology. Invest Ophthalmol Vis Sci.41:3200–3209, 2000.

Keywords: electroretinography: non–clinical • photoreceptors • transgenics/knock–outs 
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