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Xue-Jiao Chen, Kun-Chao Wu, Chang-Jun Zhang, Zi-Bing Jin; Sulfamethazine impairs retinal function by interruption of microRNA activity. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3072.
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© ARVO (1962-2015); The Authors (2016-present)
Antibiotics has made an epoch in the history for fighting against bacterial infections in human and has been commonly used in livestock to treat animal infections and improve production. However, the studies of some antibiotics on nervous system in mammals are rare and the underlying mechanism is poorly understood.
Electroretinogram (ERG) was carried out to determine the retinal function of mammals. Fundus photographs, Optical coherence tomography (OCT), immunostaining and electron microscopy were performed to investigate the retinal structure. QPCR and western blotting were conducted to detect related genes expression. Luciferase reporter assay validated the sulfamethazine on miRNA function. The relationship between sulfamethazine and target protein were revealed through Auto duck software and SPR in vitro.
Herein we show that a short-term oral administration of veterinary antibiotic sulfamethazine (SM2) would lead to significant residue in retina and thereafter retinal dysfunction in mice, guinea pig and non-human primate. Furthermore, we observe that pregnant mice intaking SM2 results in apparent retinal damage in the offsprings. We demonstrate that SM2 interrupt miRNA activity through binding to Ago2 directly in vitro, which was further confirmed by Surface plasmon resonance (SPR). Using AAV mediated si-Ago2 in mice retina, we find Ago2 is indispensable for the maintenance of retinal structure and function.
Our results discover that SM2 endanger retinal function through targeting on Ago2, implicating a potential side effect of residual sulfamethazine in human dietary meat derived from food-producing animals worldwide.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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