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Shigeki Machida, Mineo Kondo, Jeffrey A. Jamison, Naheed W. Khan, Laureen T. Kononen, Takeshi Sugawara, Ronald A. Bush, Paul A. Sieving; P23H Rhodopsin Transgenic Rat: Correlation of Retinal Function with Histopathology. Invest. Ophthalmol. Vis. Sci. 2000;41(10):3200-3209.
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purpose. To correlate retinal functional changes with structural changes in P23H
rhodopsin transgenic rats as a model of autosomal dominant retinitis
methods. P23H heterozygote (lines 1 and 3) and Sprague–Dawley control rats were
studied at 4 to 29 weeks by retinal histology, electroretinogram (ERG),
and a-wave transduction modeling.
results. Both line 1 (faster degeneration) and line 3 (slower degeneration)
showed progressive rod outer segment (ROS) shortening and outer nuclear
layer (ONL) cell loss with age. ERG b-wave maximum amplitude
(Vbmax) decreased with age, but b-wave threshold remained
constant within each line despite progressive ONL thinning and ROS
shortening. The only exception was in line 1 at 29 weeks, which showed
a slight threshold change relative to earlier ages. Vamax and a-wave threshold changed more rapidly and were more sensitive than
the b-wave in reflecting histologic degeneration. Vamax was
linearly proportional to the product of (ROS × ONL) across a two
log unit range of data combined from both lines. The photopic b-wave
was normal for both lines until the ONL thinned beyond 50%.
Phototransduction sensitivity was normal for both lines, and
dark-adaptation recovery after bleaching rhodopsin was normal.
conclusions. The P23H transgenic rat has a slow rod degeneration with initially
normal cone function, consistent with clinical findings of P23H
patients. However, the normal bleach recovery and the normal
phototransduction sensitivity in this rat model are different from
human P23H disease. a-Wave measures were more sensitive than the b-wave
for tracking changes. b-Wave threshold was inexplicably poor for
tracking degeneration. Although line 1 degenerated faster than line 3,
the functional–structural correlates were the same. The tight linear
relationship between saturated a-wave amplitude and the product of
(ROS × ONL) indicates that the density of cGMP-gated channels per
unit ROS plasma membrane area remains constant over a wide range of
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