title: Developing Stage-dependent Retinal Toxicity Induced by l-glutamate in Neonatal Rats.
abstract: The neurotransmitter glutamate causes excitotoxicity in the human retina. In neonatal rats, the degree of glutamate-induced retinal damage depends on age at administration. To elucidate the sensitivity to glutamate on various developing stage of retina, we investigated glutamate-induced retinal damage and glutamate target cells on each postnatal day (PND). Newborn rats received a single subcutaneous administration of l-glutamate on PNDs 1 to 14. Retinal cell apoptosis characterized as pyknotic and terminal deoxynucleotidyl transferase-mediated dUTP digoxigenin nick end labeling-positive nuclei was analyzed at 6 hr after treatment, and sequential morphological features of retina were evaluated on PND 21. The inner retina on PND 21 exhibited thinning in rats treated after PND 2. The thinning was most severe in rats treated on PND 8 and the number of apoptotic cells also peaked. No thinning was observed in rats treated on PND 14. In the inner nuclear layer, glutamate target cells were mainly amacrine cells; additionally, bipolar cells and horizontal cells were damaged on PND 8. These retinal changes were more severe in central retina than those in peripheral retina on PND 8. Our findings indicate the morphological consequences of glutamate-induced retinal excitotoxicity and glutamate target cells on each PND and reveal that glutamate-induced retinal damage depends on developing stage.
authors.affiliation: 1 Drug Safety Research Labs, Astellas Pharma Inc., Tsukuba, Japan.|2 Laboratory of Veterinary Pathology, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Izumisano, Japan.
authors.forename: Hikaru
authors.initials: H
authors.lastname: Mitori
authors.affiliation: 2 Laboratory of Veterinary Pathology, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Izumisano, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Izawa
authors.affiliation: 2 Laboratory of Veterinary Pathology, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Izumisano, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Kuwamura
authors.affiliation: 1 Drug Safety Research Labs, Astellas Pharma Inc., Tsukuba, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Matsumoto
authors.affiliation: 2 Laboratory of Veterinary Pathology, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Izumisano, Japan.
authors.forename: Jyoji
authors.initials: J
authors.lastname: Yamate
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects*; D018698:Glutamic Acid / Q000633:toxicity*; D007279:Injections, Subcutaneous; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000187:drug effects* / Q000254:growth & development / Q000473:pathology; D012162:Retinal Degeneration / Q000139:chemically induced* / Q000473:pathology; D055211:Retinal Photoreceptor Cell Inner Segment / Q000187:drug effects / Q000473:pathology
chemical_list: D018698:Glutamic Acid
keywords: excitotoxicity; glutamate; neonatal rat; postnatal day; retinal damage