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Retinal morphological and functional changes in an animal model of retinitis pigmentosa

Published online by Cambridge University Press:  19 March 2013

BIN LU ,
CATHERINE W. MORGANS ,
SERGEY GIRMAN ,
RAYMOND LUND  and
SHAOMEI WANG
BIN LU
Affiliation:
Regenerative Medicine Institute, Department of Biomedical Science, Cedars-Sinai Medical Center, Los Angeles, California
CATHERINE W. MORGANS
Affiliation:
Department of Physiology & Pharmacology, OHSU, Portland, Oregon
SERGEY GIRMAN
Affiliation:
Regenerative Medicine Institute, Department of Biomedical Science, Cedars-Sinai Medical Center, Los Angeles, California
RAYMOND LUND
Affiliation:
Moran Eye Center, University of Utah, Salt Lake City, Utah
SHAOMEI WANG*
Affiliation:
Regenerative Medicine Institute, Department of Biomedical Science, Cedars-Sinai Medical Center, Los Angeles, California
*
*Address correspondence and reprint requests to: Shaomei Wang, Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048. E-mail: [email protected]
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Abstract

The P23H-1 transgenic rat carries a mutated mouse opsin gene, in addition to endogenous opsin genes, and undergoes progressive photoreceptor loss that is generally characteristic of human autosomal dominant retinitis pigmentosa (RP). Here, we examined morphological changes correlated with visual function that is comparable to clinical application in the pigmented P23H-1 rat retina as photoreceptor degeneration progressed. We found that rod function was compromised as early as postnatal day 28 and was a good indicator for tracking retinal degeneration. Cone function was normal and did not change until the thickness of the photoreceptor layer was reduced by 75%. Similar to the threshold versus intensity curves used to evaluate vision of RP patients, light-adaptation curves showed that cone thresholds depended on the number of remaining functioning cones, but not on its length of outer segments (OS). By 1 year of age, both rod and cone functions were significantly compromised. Correlating with early abnormal rod function, rods and related secondary neurons also underwent progressive degeneration, including shortening of inner and OS of photoreceptors, loss of rod bipolar and horizontal cell dendrites, thickening of the outer Müller cell processes, and reduced density of pre- and postsynaptic markers. Similar early morphological modifications were also observed in cones and their related secondary neurons. However, cone function was maintained at nearly normal level for a long period. The dramatic loss of rods at late stage of degeneration may contribute to the dysfunction of cones. Attention has to be focused on preserving cone function and identifying factors that damage cones when therapeutic regimes are applied to treat retinal degeneration. As such, these findings provide a foundation for future studies involving treatments to counter photoreceptor loss.

Keywords

P23H mutationRetinitis pigmentosaRetinal degenerationRod and coneVisual function
Type
Research Articles
Information
Visual Neuroscience , Volume 30 , Issue 3 , May 2013 , pp. 77 - 89
Copyright
Copyright © Cambridge University Press 2013 

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