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As a powerful psychostimulant with high potential for abuse, methamphetamine (Meth) could cause long-lasting abnormalities in retinas. The purpose of this study was to investigate the effects of systemic administration of Meth at low dose on retinal damage and understand the underlying mechanisms of pathology. CD1 mice were treated with 0.5 mg/kg or 1 mg/kg Meth by intraperitoneal injection daily for 2 months, mice treated with saline were used as negative control. Electroretinography (ERG) reflects the mass response of photoreceptor cells and was used to test the outer retinal function after Meth treatment. Toluidine blue staining was used to show the retinal morphology and evaluate the photoreceptor cell loss. Inflammatory factors were measured by enzyme-linked immunosorbent assay to show the inflammatory response. Terminal deoxynucleotidyl transferase dUTP Nick end labeling assay was used to detect the apoptosis-positive cells. Real-time polymerase chain reaction and Western blot were applied to measure the gene and protein change to explore the underlying mechanisms. Results demonstrated that retinal damage was caused by Meth treatment after 2 months, evidenced by loss of rod photoreceptor cells; decreased ERG amplitude; increased apoptotic photoreceptor cells, cytochrome-c release, caspase-3 activity, caspase-9 activity, and apoptosis-related protein expression; increased malondialdehyde level as well as nicotinamide adenine dinucleotide phosphate oxidase 4 protein expression; decreased anti-oxidative agents glutathione as well as superoxide dismutase levels; and increased production and gene expression of inflammatory factors. Our study indicated that systemic administration of Meth caused neurotoxic effects on CD1 mouse retinas, providing the potential mechanisms for the retina damage caused by Meth abuse.

Objective. Insulin resistance (IR) plays a key role in gestational diabetes mellitus (GDM) pathogenesis. The antiaging protein klotho has been proven to be closely related to IR. The purpose of this study was to investigate the effect of klotho on IR in GDM trophoblast cells. Methods. The GDM cell model of HTR-8/SVneo cells was induced by high glucose (HG). Plasmid transfection was used to mediate the overexpression or silencing of klotho. The effects of klotho on cell viability, IR, and the IGF-1/PI3K pathways were observed by RT-qPCR, western blot, Cell Counting Kit-8 detection, glucose uptake assay, and immunofluorescence detection. Results. Klotho expression was up-regulated in HG-induced cells. Overexpression of klotho could reduce the cell viability, insulin signaling molecules (INSR-α, INSR-β, IRS1, IRS2, and GLUT4), and glucose uptake in HTR-8/SVneo cells of the HG group. In addition, the overexpression of klotho inhibited the levels of IGF-1, IGF-1R/p-IGF-1R, and the phosphorylation and activation of the signal transduction molecules PI3K/Akt/mTOR. On the contrary, klotho deletions could reverse these changes of HTR-8/SVneo cells induced by HG. Conclusion. In a word, the results of this study showed that the regulation of klotho played an important role in the IR of trophoblast cells induced by HG, which was mediated at least in part by the IGF-1/PI3K/Akt/mTOR pathway.