Functional and structural changes in the retina of wire-haired dachshunds with early-onset cone-rod dystrophy.
OBJECTIVE
To describe and classify the morphologic changes in a naturally occurring dog model of early-onset cone-rod dystrophy (CRD) and to correlate these with earlier described clinical characteristics of the disease in dogs.


METHODS
Purpose-bred Standard Wire-Haired Dachshunds (SWHDs) derived from a large pedigree of dogs with early-onset CRD were euthanatized at defined ages to characterize morphologic changes in the disease process. Specimens were examined by light microscopy, including morphometric studies, electron microscopy, and immunohistochemistry. Peanut agglutinin (PNA), protein kinase C (PKC), synaptophysin (Syn), rhodopsin (Rho)-63, glial fibrillary acidic protein (GFAP), and short-wavelength cone opsin (OS) were used for immunohistochemical characterization.


RESULTS
The photopic cone-system-derived ERG amplitudes were already significantly reduced or nonrecordable in CRD-affected dogs at 5 weeks, the earliest age studied. The outer retina was morphologically most severely affected initially, with a subsequent degeneration of the inner retina. Cone degeneration was more pronounced than rod degeneration in young CRD-affected dogs. There was a marked phenotypic variation based on morphologic findings in the affected dogs. At the earliest time point studied (5-8 weeks) cone photoreceptor and glial cell abnormalities were observed, in accordance with earlier studies based on electrophysiological and clinical findings in which day blindness and abnormal cone ERGs were observed in young affected SWHD puppies. Preliminary genetic studies have indicated an autosomal recessive mode of inheritance for the defect.


CONCLUSIONS
Through functional and structural characterization, early-onset cone abnormalities were found, consistent with a cone dysplasia at an age when rod structure was normal. Further studies are in progress to identify the gene(s) involved in this retinal disease process. The presently described natural animal model of primary cone dysplasia followed by rod degeneration may provide further insight into the human counterpart. Further studies are needed to ascertain an autosomal recessive mode of inheritance for CRD in the SWHD.
Ropstad
Ernst O
EO
Department of Companion Animal Clinical Sciences, Division of Genetics, Norwegian University School of Veterinary Science, Oslo, Norway. ernst.ropstad@veths.no
Narfström
Kristina
K
Lingaas
Frode
F
Wiik
Caroline
C
Bruun
Anitha
A
Bjerkås
Ellen
E
D000818:Animals; D004195:Disease Models, Animal; D004283:Dog Diseases / Q000378:metabolism / Q000503:physiopathology*; D004285:Dogs; D004596:Electroretinography / Q000662:veterinary*; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D008297:Male; D008854:Microscopy, Electron; D010375:Pedigree; D010641:Phenotype; D020419:Photoreceptor Cells, Vertebrate / Q000502:physiology / Q000648:ultrastructure; D011493:Protein Kinase C / Q000378:metabolism; D012160:Retina / Q000378:metabolism / Q000503:physiopathology* / Q000648:ultrastructure*; D012162:Retinal Degeneration / Q000378:metabolism / Q000503:physiopathology / Q000662:veterinary*; D012243:Rhodopsin / Q000378:metabolism; D017299:Rod Opsins / Q000378:metabolism; D016708:Synaptophysin / Q000378:metabolism
D005904:Glial Fibrillary Acidic Protein; D017299:Rod Opsins; D016708:Synaptophysin; D012243:Rhodopsin; D011493:Protein Kinase C