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Lamivudine Inhibits RNA-induced Retinal Pigment Epithelium Degeneration via Anti-inflammatory and Anti-senescence Activities. | LitMetric
Purpose : Accumulation of the long noncoding element RNA activates the NLRP3 inflammasome and leads to retinal pigment epithelium (RPE) cell death, a key event in the pathogenesis of geographic atrophy during late-stage age-related macular degeneration. Lamivudine (3TC) is a nucleoside analog reverse transcriptase inhibitor known to inhibit the NLRP3 inflammasome. Currently, the intracellular response of the senescence marker p16 to the long noncoding RNA is being actively studied. The present study aimed to assess the efficacy of 3TC against RNA-induced RPE inflammation and senescence by evaluating changes in expression of the proinflammatory cytokines IL-18 and IL-1β and of p16 in RPE cells.Methods : Cultured human RPE cells and in vivo mouse RPE cells were transfected with an in vitro-transcribed RNA, and changes in IL-18, IL-1β, and p16 expression measured in the presences of 3TC or 3,4-(M)CA as a negative control.Results : Treatment with 3TC markedly reduced RNA-induced expression of IL-18 and IL-1β in human and mouse RPE cells compared with the negative control. Further, RNA-induced p16 expression was suppressed by 3TC in human RPE cells.Conclusions : Our data suggest that RNA accumulation contributes to RPE cell senescence in age-related macular degeneration and that this pathogenic process can be suppressed by 3TC.Translational Relevance : Further verifying this study leads to potential targets for age-related macular degeneration therapy.
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