NLRP3 has a protective role in age-related macular degeneration through the induction of IL-18 by drusen components.
NLRP3 has a protective role in age-related macular degeneration through the induction of IL-18 by drusen components.
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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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影响因子：
15.9
作者：
Coughlin, CM;Salhany, KE;Lee, WMF
通讯作者：
Lee, WMF
DOI：
10.1097/iae.0b013e3181e9f942
发表时间：
2010-11-01
影响因子：
3.3
作者：
Arias, Luis;Caminal, Jose M.;Pujol, Octavio
通讯作者：
Pujol, Octavio
影响因子：
30.5
作者：
通讯作者：
--
影响因子：
9.8
作者：
Edwards, Albert O.;Malek, Goldis
通讯作者：
Malek, Goldis
DOI：
10.1073/pnas.222551899
发表时间：
2002-11-12
影响因子：
11.1
作者：
Crabb, JW;Miyagi, M;Hollyfield, JG
通讯作者：
Hollyfield, JG