NLRP3 Upregulation in Retinal Pigment Epithelium in Age-Related Macular Degeneration
AbstractInflammation and oxidative stress are involved in age-related macular degeneration (AMD) and possibly associated with an activation of neuronal apoptosis inhibitor protein/class II transcription activator of the Major Histocompatibility Complex (MHC)/heterokaryon incompatibility/telomerase-associated protein 1, leucine-rich repeat or nucleotide-binding domain, leucine-rich repeat-containing family, and pyrin domain-containing 3 (NLRP3) inflammasome. In the present study, we used a translational approach to address this hypothesis. In patients with AMD, we observed increased mRNA levels of NLRP3, pro-interleukin-1 beta (IL-1β) and pro-IL-18 in AMD lesions of the retinal pigment epithelium (RPE) and photoreceptor. In vitro, a similar increase was evoked by oxidative stress or lipopolysaccharide (LPS) stimulation in the adult retinal pigment epithelium (ARPE-19) cell line, and the increase was reduced in siRNA transfected cells to knockdown NLRP3. Ultrastructural studies of ARPE-19 cells showed a swelling of the cytoplasm, mitochondrial damage, and occurrence of autophagosome-like structures. NLRP3 positive dots were detected within autophagosome-like structures or in the extracellular space. Next, we used a mouse model of AMD, Ccl2/Cx3cr1 double knockout on rd8 background (DKO rd8) to ascertain the in vivo relevance. Ultrastructural studies of the RPE of these mice showed damaged mitochondria, autophagosome-like structures, and cytoplasmic vacuoles, which are reminiscent of the pathology seen in stressed ARPE-19 cells. The data suggest that the NLRP3 inflammasome may contribute in AMD pathogenesis. View Full-Text
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Wang, Y.; Hanus, J.W.; Abu-Asab, M.S.; Shen, D.; Ogilvy, A.; Ou, J.; Chu, X.K.; Shi, G.; Li, W.; Wang, S.; Chan, C.-C. NLRP3 Upregulation in Retinal Pigment Epithelium in Age-Related Macular Degeneration. Int. J. Mol. Sci. 2016, 17, 73.
Wang Y, Hanus JW, Abu-Asab MS, Shen D, Ogilvy A, Ou J, Chu XK, Shi G, Li W, Wang S, Chan C-C. NLRP3 Upregulation in Retinal Pigment Epithelium in Age-Related Macular Degeneration. International Journal of Molecular Sciences. 2016; 17(1):73.Chicago/Turabian Style
Wang, Yujuan; Hanus, Jakub W.; Abu-Asab, Mones S.; Shen, Defen; Ogilvy, Alexander; Ou, Jingxing; Chu, Xi K.; Shi, Guangpu; Li, Wei; Wang, Shusheng; Chan, Chi-Chao. 2016. "NLRP3 Upregulation in Retinal Pigment Epithelium in Age-Related Macular Degeneration." Int. J. Mol. Sci. 17, no. 1: 73.
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