Functional and structural changes in the retina of wire-haired dachshunds with early-onset cone-rod dystrophy

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Functional and structural changes in the retina of wire-haired dachshunds with early-onset cone-rod dystrophy. / Ropstad, Ernst O; Narfstrom, Kristina; Lingaas, Frode; Wiik, Caroline; Bruun, Anitha; Bjerkas, Ellen.

In: Investigative Ophthalmology & Visual Science, Vol. 49, No. 3, 2008, p. 1106-1115.

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Ropstad, Ernst O ; Narfstrom, Kristina ; Lingaas, Frode ; Wiik, Caroline ; Bruun, Anitha ; Bjerkas, Ellen. / Functional and structural changes in the retina of wire-haired dachshunds with early-onset cone-rod dystrophy. In: Investigative Ophthalmology & Visual Science. 2008 ; Vol. 49, No. 3. pp. 1106-1115.

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TY - JOUR

T1 - Functional and structural changes in the retina of wire-haired dachshunds with early-onset cone-rod dystrophy

AU - Ropstad, Ernst O

AU - Narfstrom, Kristina

AU - Lingaas, Frode

AU - Wiik, Caroline

AU - Bruun, Anitha

AU - Bjerkas, Ellen

PY - 2008

Y1 - 2008

N2 - PURPOSE. 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 earlyonset 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.

AB - PURPOSE. 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 earlyonset 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.

U2 - 10.1167/iovs.07-0848

DO - 10.1167/iovs.07-0848

M3 - Article

VL - 49

SP - 1106

EP - 1115

JO - Investigative Ophthalmology & Visual Science

T2 - Investigative Ophthalmology & Visual Science

JF - Investigative Ophthalmology & Visual Science

SN - 1552-5783

IS - 3

ER -