A Transient Developmental Background Finding in the Retina Observed in Neonatal Dogs in Juvenile Toxicology Studies

Author:

Petruska Janet M.1,Remick Amera K.2,Lejeune Typhaine3,Vezina Mark3,Robinson Keith3,Bussières Martin4,Gilger Brian C.5,Dubielzig Richard R.6

Affiliation:

1. PTC Therapeutics, Inc., South Plainfield, New Jersey, USA

2. Charles River Laboratories, Durham, North Carolina, USA

3. Charles River Laboratories Montreal ULC, Senneville, Quebec, Canada

4. V&O Services, Saint-Lazare, Quebec, Canada

5. North Carolina State University, Raleigh, North Carolina, USA

6. Ocular Services on Demand, University of Wisconsin School of Veterinary Medicine, Madison, Wisconsin, USA

Abstract

In a juvenile toxicology program, an unexpected finding of vacuolation of inner nuclear, ganglion cell, and nerve fiber layers of the retina was observed microscopically in routine Davidson’s fixed and hematoxylin and eosin–stained tissue sections of eyes in beagle dogs at approximately 5 weeks of age. There was no necrosis or degeneration of the affected cells and no associated inflammation. Fluorescein angiography revealed no vascular leakage. Optical coherence tomography (OCT) indicated swollen cells in the same layers of the retina as observed at light microscopic examination. Transmission electron microscopy revealed that the retinal vacuolation likely was consistent with intracellular swelling of amacrine, horizontal, and/or bipolar cells of the inner nuclear layer as affected cells had an expanded cytoplasm but contained normal nucleus and organelles. As assessed by animal behavior and full-field electroretinography, the retinal vacuolation appeared to have no impact on visual function. Retinal vacuolation was seen in approximately 40% of dogs at 5 weeks of age using OCT and/or light microscopic examination. Because the change was transient and age related, did not result in degenerative retinal changes, and was not present in dogs older than 5 weeks of age, it was considered a background developmental observation in beagle dogs.

Publisher

SAGE Publications

Subject

Cell Biology,Toxicology,Molecular Biology,Pathology and Forensic Medicine

Reference21 articles.

1. Canine Retina Has a Primate Fovea-Like Bouquet of Cone Photoreceptors Which Is Affected by Inherited Macular Degenerations

2. Ocular Toxicity Assessment From Systemically Administered Xenobiotics

3. Committee for Human Medicinal Products, European Medicines Agency. (2008). Guideline on the need for non-clinical testing in juvenile animals of pharmaceuticals for pediatric indications. London, UK. Accessed February 28, 2015. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003305.pdf.

4. Visual System

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