Postnatal exposure to trimethyltin chloride induces retinal developmental neurotoxicity in mice via glutamate and its transporter related changes.

Autor: Kim J; College of Veterinary Medicine, Konkuk University, Seoul, Republic of Korea., Ryu B; Department of Biomedical Informatics, College of Applied Life Sciences, Jeju National University, Jeju, Republic of Korea., Bang J; Laboratory Animal Medicine, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea., Kim CY; College of Veterinary Medicine, Konkuk University, Seoul, Republic of Korea. Electronic address: vivavet@konkuk.ac.kr., Park JH; Laboratory Animal Medicine, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea. Electronic address: pjhak@snu.ac.kr.
Jazyk: angličtina
Zdroj: Reproductive toxicology (Elmsford, N.Y.) [Reprod Toxicol] 2023 Aug; Vol. 119, pp. 108395. Date of Electronic Publication: 2023 May 09.
DOI: 10.1016/j.reprotox.2023.108395
Abstrakt: Exposure to toxic substances during postnatal period is one of the major factors causing retinal developmental defects. The developmental toxicity of trimethyltin chloride (TMT), a byproduct of an organotin compound widely used in agriculture and industrial fields, has been reported; however, the effect on the mammalian retina during postnatal development and the mechanism have not been elucidated to date. We exposed 0.75 and 1.5 mg/kg of TMT to neonatal ICR mice (1:1 ratio of male and female) up to postnatal day 14 and performed analysis of the retina: histopathology, apoptosis, electrophysiological function, glutamate concentration, gene expression, and fluorescence immunostaining. Exposure to TMT caused delayed eye opening, eye growth defect and thinning of retinal layer. In addition, apoptosis occurred in the retina along with b-wave and spiking activity changes in the micro-electroretinogram. These changes were accompanied by an increase in the concentration of glutamate, upregulation of astrocyte-related genes, and increased expression of glial excitatory amino acid transporter (EAAT) 1 and 2. Conversely, EAAT 3, 4, and 5, mainly located in the neurons, were decreased. Our results are the first to prove postnatal retinal developmental neurotoxicity of TMT at the mammalian model and analyze the molecular, functional as well as morphological aspects to elucidate possible mechanisms: glutamate toxicity with EAAT expression changes. These mechanisms may suggest not only a strategy to treat but also a clue to prevent postnatal retina developmental toxicity of toxic substances.
Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: C-Yoon Kim reports financial support was provided by Ministry of Food and Drug Safety. C-Yoon Kim reports financial support was provided by National Research Foundation of Korea.
(Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: