Vet Pathol Download to Citation Manager
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Fix, A. S.
Right arrow Articles by Tizzano, J. P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Fix, A. S.
Right arrow Articles by Tizzano, J. P.

Veterinary Pathology, Vol 32, Issue 5 521-531, Copyright © 1995 by American College of Veterinary Pathologists

ARTICLES

Progressive retinal toxicity in neonatal rats treated with D,L-2-amino-3-phosphonopropionate (D,L-AP3)

A. S. Fix, J. W. Horn, R. L. Hall, J. A. Johnson and J. P. Tizzano
Toxicology Research Laboratories, Lilly Research Laboratories, Eli Lilly and Company, Greenfield, IN, USA.

D,L-2-amino-3-phosphonopropionate (D,L-AP3) has complex pharmacologic activity at central nervous system metabotropic glutamate receptors important in excitatory neurotransmission and development. Previous studies have described retinal and optic nerve atrophy in adult rats after postnatal treatment with D,L-AP3. Using neonatal male Sprague-Dawley rats, the present studies examined normal postnatal retinal development (n = 20) and the progression of retinal toxicity induced by D,L-AP3 (n = 30). Retinal development was examined by light microscopy on postnatal days (PNDs) 5, 9, 12, 16, and 22. Between PNDs 5 and 16, the retina underwent considerable postnatal differentiation. A prominent neuroblastic layer evident on PND 5 differentiated into outer retinal layers by PND 16. To examine the effects of D,L-AP3, neonatal rats were treated intraperitoneally with sterile water or 400 mg/kg/day D,L-AP3 on PNDs 3-6. On PNDs 5, 7, 10, 15, and 20, retinas were examined by light and electron microscopy. On PNDs 5 and 7, cells with swollen, pale cytoplasm were evident in the more differentiated inner nuclear layer and in the middle of the developing neuroblastic layer. Retinal toxicity rapidly progressed after treatment, because developing outer retinal layers had cytoplasmic swelling, nuclear pyknosis, and necrosis on PND 10. By PNDs 15 and 20, retinal dystrophy was severe and involved primarily outer layers. This study showed that early postnatal treatment with D,L-AP3 initiates rapidly progressing retinal toxicity, thus implicating metabotropic glutamate receptors in the postnatal retinal development of rats.


This article has been cited by other articles:


Home page
 Toxicol PatholHome page
A. S. Fix and R. H. Garman
Practical Aspects of Neuropathology: A Technical Guide for Working with the Nervous System
Toxicol Pathol, January 1, 2000; 28(1): 122 - 131.
[Abstract] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 1995 by the American College of Veterinary Pathologists.