IOVS
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published In Press as doi:10.1167/iovs.08-1712 on March 14, 2008
 (Investigative Ophthalmology and Visual Science. 2008;49:2686-2695.)
© 2008 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.08-1712
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
iovs.08-1712v1
49/6/2686    most recent
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Google Scholar
Right arrow Articles by Katz, M. L.
Right arrow Articles by Narfström, K.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Katz, M. L.
Right arrow Articles by Narfström, K.

Retinal Pathology in a Canine Model of Late Infantile Neuronal Ceroid Lipofuscinosis

Martin L. Katz,1,2 Joan R. Coates,3 Jocelyn J. Cooper,3,4 Dennis P. O'Brien,3 Manbok Jeong,3,5,6 and Kristina Narfström1,3

1From the Mason Eye Institute, University of Missouri School of Medicine, the 2Departments of Veterinary Pathobiology and 3Medicine and Surgery, University of Missouri, College of Veterinary Medicine, Columbia, Missouri; and the 5Department of Veterinary Surgery and Ophthalmology, College of Veterinary Medicine, and 6BK21 Program for Veterinary Science, Seoul National University, Seoul, Republic of Korea.

PURPOSE. Late infantile neuronal ceroid lipofuscinosis (NCL) is an inherited disorder characterized by progressive vision loss. The disease results from mutations in the TPP1 (CLN2) gene. Studies were undertaken to characterize the effects of a TPP1 frameshift mutation on the retina in Dachshunds.

METHODS. A litter of four puppies consisting of one homozygous affected dog, two heterozygotes, and one homozygous normal dog were monitored for neurologic and retinal changes through 10 months of age. The affected and homozygous normal dogs, as well as one of the heterozygotes, were then euthanatized, and the retinas were examined morphologically.

RESULTS. The affected dog exhibited normal visual behavior and retinal function at 3 months of age, but vision was clearly impaired by 7 months, with markedly reduced ERG b-wave amplitudes. Beyond 7 months of age, the affected dog was functionally blind, and pupillary light reflexes and ERG response amplitudes continued to decline through 10 months of age. Both rod and cone system functions were severely impaired. The retina exhibited accumulation of autofluorescent storage bodies with distinctive curvilinear contents. Substantial cell loss occurred in the inner nuclear layer, with a smaller reduction in photoreceptor cell density.

CONCLUSIONS. The canine TPP1 mutation results in progressive vision loss and retinal degeneration similar to that which occurs in human late infantile NCL. With the canine model, the natural history of disease progression in the retina provides a better understanding of the pathologic course of the disease and provides objective markers that can be used to assess the efficacy of therapeutic interventions.






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2008 by the Association for Research in Vision and Ophthalmology