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• W2328231397 endingPage "514" @default.
• W2328231397 startingPage "505" @default.
• W2328231397 abstract "Purpose.: To investigate whether activation of Toll-like receptor 3 (TLR3) promotes the degeneration of retinal ganglion cells (RGCs) by upregulating the protein levels of c-jun N-terminal kinase 3 (JNK3). Methods.: Toll-like receptor 3-specific activator, Poly(I:C) (polyinosinic-polycytidylic acid), or PBS was injected into the vitreous humor of Thy1-YFP mice. At 24, 48, and 72 hours after treatments, degeneration of RGCs was assessed by using antibodies against brain-specific homeobox/POU domain protein 3a (Brn3a). A TLR3-specific inhibitor was injected into the vitreous humor with or without Poly(I:C). Western blot assays were performed to determine relative levels of TLR3, JNK3, pJNK3, and sterile alpha and HEAT/Armadillo motif-containing 1 (SARM1) proteins in retinal protein extracts, and immunohistochemistry assays were performed to determine their cellular localization in the retina. Mouse eyes were treated with Poly(I:C) or PBS along with MitoTracker Red, and colocalization of MitoTracker Red and JNK3 in the retinas was determined by using antibodies against JNK3. Results.: Poly(I:C) activated TLR3 and upregulated its downstream target protein JNK3 but not SARM1 in the retina. Poly(I:C) activated TLR3 and upregulated JNK3 specifically in RGCs and promoted a significant degeneration of RGCs over a 72-hour time period. Toll-like receptor 3 upregulated the levels of JNK3 protein in the cytoplasm of RGCs, but not in the mitochondria. Toll-like receptor 3-specific inhibitor downregulated Poly(I:C)-mediated upregulation of JNK3 protein, and, in turn, significantly attenuated TLR3-induced degeneration of RGCs. Conclusions.: Results presented in this study show that the activation of TLR3 alone promotes the degeneration of RGCs by upregulating the protein levels of JNK3." @default.
• W2328231397 created "2016-06-24" @default.
• W2328231397 creator A5005517312 @default.
• W2328231397 creator A5051409764 @default.
• W2328231397 creator A5082982166 @default.
• W2328231397 date "2015-01-06" @default.
• W2328231397 modified "2023-10-17" @default.
• W2328231397 title "Activation of TLR3 Promotes the Degeneration of Retinal Ganglion Cells by Upregulating the Protein Levels of JNK3" @default.
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• W2328231397 doi "https://doi.org/10.1167/iovs.14-15539" @default.
• W2328231397 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4299467" @default.
• W2328231397 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/25564448" @default.
• W2328231397 hasPublicationYear "2015" @default.
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