Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Invest Ophthalmol Vis Sci. 2009 Feb;50(2):801-13. doi: 10.1167/iovs.08-2562. Epub 2008 Sep 4.

Characterization of a canine model of autosomal recessive retinitis pigmentosa due to a PDE6A mutation.

Author information

  • 1Department of Small Animal Clinical Studies, Michigan State University, East Lansing, Michigan 48824, USA.

Abstract

PURPOSE:

To characterize a canine model of autosomal recessive RP due to a PDE6A gene mutation.

METHODS:

Affected and breed- and age-matched control puppies were studied by electroretinography (ERG), light and electron microscopy, immunohistochemistry, and assay for retinal PDE6 levels and enzymatic activity.

RESULTS:

The mutant puppies failed to develop normal rod-mediated ERG responses and had reduced light-adapted a-wave amplitudes from an early age. The residual ERG waveforms originated primarily from cone-driven responses. Development of photoreceptor outer segments stopped, and rod cells were lost by apoptosis. Immunohistochemistry demonstrated a marked reduction in rod opsin immunostaining outer segments and relative preservation of cones early in the disease process. With exception of rod bipolar cells, which appeared to be reduced in number relatively early in the disease process, other inner retinal cells were preserved in the early stages of the disease, although there was marked and early activation of Müller glia. Western blot analysis showed that the PDE6A mutation not only resulted in a lack of PDE6A protein but the affected retinas also lacked the other PDE6 subunits, suggesting expression of PDE6A is essential for normal expression of PDE6B and PDE6G. Affected retinas lacked PDE6 enzymatic activity.

CONCLUSIONS:

This represents the first characterization of a PDE6A model of autosomal recessive retinitis pigmentosa, and the PDE6A mutant dog shows promise as a large animal model for investigation of therapies to rescue mutant rod photoreceptors and to preserve cone photoreceptors in the face of a rapid loss of rod cells.

PMID:
18775863
[PubMed - indexed for MEDLINE]
PMCID:
PMC3720143
Free PMC Article

Images from this publication.See all images (10)Free text

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Figure 9
Figure 10
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk