The Neuroprotective Effect of Rapamycin as a Modulator of the mTOR-NF-κB Axis during Retinal Inflammation

PloS One
Tomohiro OkamotoKazuo Tsubota

Abstract

The determination of the molecular mechanism underlying retinal pathogenesis and visual dysfunction during innate inflammation, and the treatment effect of rapamycin thereon. The endotoxin-induced uveitis and retinitis mouse model was established by injecting lipopolysaccharide. The mice were subsequently treated with rapamycin, a mammalian target of rapamycin (mTOR) inhibitor. The rhodopsin mRNA and protein expression level in the retina and the photoreceptor outer segment (OS) length in immunohistochemical stainings were measured, and visual function was recorded by electroretinography. Inflammatory cytokines, their related molecules, mTOR, and LC3 levels were measured by real-time PCR and/or immunoblotting. Leukocyte adhesion during inflammation was analyzed using concanavalin A lectin. The post-transcriptional reduction in the visual pigment of rod photoreceptor cells, rhodopsin, OS shortening, and rod photoreceptor cell dysfunction during inflammation were suppressed by rapamycin. Activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and induction of inflammatory cytokines, such as interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1), and the activation of the downstream signal...Continue Reading

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Citations

Feb 23, 2020·Investigative Ophthalmology & Visual Science·Chenyu LiJiaqian Jiang
Feb 25, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Hirohiko KawashimaKazuo Tsubota
Aug 21, 2019·Cells·Maurizio CammalleriPaola Bagnoli
Mar 12, 2021·Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics·Pedro Javier Salas-AmbrosioGustavo Adolfo García-Sánchez
Jul 11, 2021·Experimental Eye Research·Zhanyu NiuLan Gao

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Methods Mentioned

BETA
nuclear translocation
electrophoresis
Assay
PCR
enzyme-linked immunosorbent assay

Software Mentioned

ImageJ

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