The DOI matches its Crossref record; 55 of the 55 references it cites were found in a registry or an index.
NLRP3 has a protective role in age-related macular degeneration through the induction of IL-18 by drusen components
Open accessAbstract
Age-related macular degeneration (AMD) is the leading cause of central vision loss worldwide. Drusen accumulation is the major pathological hallmark common to both dry and wet AMD. Although activation of the immune system has been implicated in disease progression, the pathways involved are unclear. Here we show that drusen isolated from donor AMD eyes activates the NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome, causing secretion of interleukin-1β (IL-1β) and IL-18. Drusen component C1Q also activates the NLRP3 inflammasome. Moreover, the oxidative-stress–related protein-modification carboxyethylpyrrole (CEP), a biomarker of AMD, primes the inflammasome. We found cleaved caspase-1 and NLRP3 in activated macrophages in the retinas of mice immunized with CEP-adducted mouse serum albumin, modeling a dry-AMD–like pathology. We show that laser-induced choroidal neovascularization (CNV), a mouse model of wet AMD, is exacerbated in Nlrp3−/− but not Il1r1−/− mice, directly implicating IL-18 in the regulation of CNV development. These findings indicate a protective role for NLRP3 and IL-18 in the progression of AMD.
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Defective LPS Signaling in C3H/HeJ and C57BL/10ScCr Mice: Mutations in Tlr4 Gene
Poltorak, A., He, X., Smirnova, I., Liu, M.-Y., Huffel, C. V., Du, X., Birdwell, D., Alejos, E., Silva, M., Galanos, C., et al. (1998) · Science · doi:10.1126/science.282.5396.2085 · Cited by 7,631
Origin and physiological roles of inflammation
Medzhitov, R. (2008) · Nature · doi:10.1038/nature07201 · Cited by 6,618
A role for mitochondria in nlrp3 inflammasome activation
Zhou, R., Yazdi, A. S., Menu, P., & Tschopp, J. (2011) · Nature · doi:10.1038/nature09663 · Cited by 5,602
Gout-associated uric acid crystals activate the NALP3 inflammasome
Martinon, F., Pétrilli, V., Mayor, A., Tardivel, A., & Tschopp, J. (2006) · Nature · doi:10.1038/nature04516 · Cited by 5,326
Global data on visual impairment in the year 2002.
(2004) · Europe PMC (PubMed Central) · Cited by 4,157
NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals
Duewell, P., Kono, H., Rayner, K. J., Sirois, C. M., Vladimer, G., Bauernfeind, F. G., Abela, G. S., Franchi, L., Nuñez, G., Schnurr, M., et al. (2010) · Nature · doi:10.1038/nature08938 · Cited by 4,026
Cryopyrin activates the inflammasome in response to toxins and ATP
Mariathasan, S., Weiss, D. S., Newton, K., McBride, J., O'Rourke, K., Roose-Girma, M., Lee, W. P., Weinrauch, Y., Monack, D. M., & Dixit, V. M. (2006) · Nature · doi:10.1038/nature04515 · Cited by 3,080
Hornung, V., Bauernfeind, F., Halle, A., Samstad, E. O., Kono, H., Rock, K. L., Fitzgerald, K. A., & Latz, E. (2008) · Nature Immunology · doi:10.1038/ni.1631 · Cited by 3,065
Thioredoxin-interacting protein links oxidative stress to inflammasome activation
Zhou, R., Tardivel, A., Thorens, B., Choi, I., & Tschopp, J. (2010) · Nature Immunology · doi:10.1038/ni.1831 · Cited by 2,708
Ranibizumab and bevacizumab for neovascular age-related macular degeneration
(2011) · New England Journal of Medicine · doi:10.1056/nejmoa1102673 · Cited by 2,669
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The interleukin-1 family: back to the future
Garlanda, C., Dinarello, C. A., & Mantovani, A. (2013) · Immunity · doi:10.1016/j.immuni.2013.11.010 · Cited by 1,945
“In some models of disease as in age-related macular degeneration, IL-18 is protective (Doyle et al., 2012).”
Overview of the IL ‐1 family in innate inflammation and acquired immunity
Dinarello, C. A. (2018) · Immunological Reviews · doi:10.1111/imr.12621 · Cited by 1,866
Interleukin-18 and IL-18 Binding Protein
Dinarello, C. A., Novick, D., Kim, S., & Kaplanski, G. (2013) · Frontiers in Immunology · doi:10.3389/fimmu.2013.00289 · Cited by 938
The impact of oxidative stress and inflammation on RPE degeneration in non-neovascular AMD
Datta, S., Cano, M., Ebrahimi, K., Wang, L., & Handa, J. T. (2017) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2017.03.002 · Cited by 802
Pharmacological Inhibitors of the NLRP3 Inflammasome
Zahid, A., Li, B., Kombe, A. J. K., Jin, T., & Tao, J. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02538 · Cited by 671
Metadata
- Authors
- Doyle, S. L., Campbell, M., Ozaki, E., Salomon, R. G., Mori, A., Kenna, P. F., Farrar, G. J., Kiang, A.-S., Humphries, M. M., Lavelle, E. C., O'Neill, L. A. J., Hollyfield, J. G., & Humphries, P.
- Venue
- Nature Medicine
- Published
- 2012-04-08
- Volume
- 18
- Issue
- 5
- Pages
- 791-798
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W1985144223
- Cited by
- 422
- References
- 55
- FWCI
- 15.80
- Type
- journal article
- Language
- en
- Open access
- green
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- Doyle, S. L., Campbell, M., Ozaki, E., Salomon, R. G., Mori, A., Kenna, P. F., Farrar, G. J., Kiang, A.-S., Humphries, M. M., Lavelle, E. C., O'Neill, L. A. J., Hollyfield, J. G., & Humphries, P. (2012). NLRP3 has a protective role in age-related macular degeneration through the induction of IL-18 by drusen components. Nature Medicine. https://doi.org/10.1038/nm.2717
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