title: NLRP3 inflammasome: activation and regulation in age-related macular degeneration.
abstract: Age-related macular degeneration (AMD) is the leading cause of legal blindness in the elderly in industrialized countries. AMD is a multifactorial disease influenced by both genetic and environmental risk factors. Progression of AMD is characterized by an increase in the number and size of drusen, extracellular deposits, which accumulate between the retinal pigment epithelium (RPE) and Bruch's membrane (BM) in outer retina. The major pathways associated with its pathogenesis include oxidative stress and inflammation in the early stages of AMD. Little is known about the interactions among these mechanisms that drive the transition from early to late stages of AMD, such as geographic atrophy (GA) or choroidal neovascularization (CNV). As part of the innate immune system, inflammasome activation has been identified in RPE cells and proposed to be a causal factor for RPE dysfunction and degeneration. Here, we will first review the classic model of inflammasome activation, then discuss the potentials of AMD-related factors to activate the inflammasome in both nonocular immune cells and RPE cells, and finally introduce several novel mechanisms for regulating the inflammasome activity.
authors.affiliation: Department of Ophthalmology and Visual Sciences, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada V5Z 3N9.
authors.forename: Jiangyuan
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Ophthalmology and Visual Sciences, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada V5Z 3N9.
authors.forename: Ruozhou Tom
authors.initials: RT
authors.lastname: Liu
authors.affiliation: Department of Ophthalmology and Visual Sciences, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada V5Z 3N9.
authors.forename: Sijia
authors.identifier: 0000-0002-4545-2997
authors.initials: S
authors.lastname: Cao
authors.affiliation: Department of Ophthalmology and Visual Sciences, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada V5Z 3N9.
authors.forename: Jing Z
authors.initials: JZ
authors.lastname: Cui
authors.affiliation: Department of Ophthalmology and Visual Sciences, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada V5Z 3N9.
authors.forename: Aikun
authors.identifier: 0000-0002-5057-8439
authors.initials: A
authors.lastname: Wang
authors.affiliation: Department of Ophthalmology and Visual Sciences, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada V5Z 3N9.
authors.forename: Eleanor
authors.identifier: 0000-0003-1837-7685
authors.initials: E
authors.lastname: To
authors.affiliation: Department of Ophthalmology and Visual Sciences, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada V5Z 3N9.
authors.forename: Joanne A
authors.initials: JA
authors.lastname: Matsubara
mesh_terms: D000818:Animals; D016570:Bruch Membrane / Q000378:metabolism / Q000473:pathology; D002352:Carrier Proteins / Q000378:metabolism*; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism*; D008268:Macular Degeneration / Q000378:metabolism* / Q000473:pathology; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D055213:Retinal Pigment Epithelium / Q000378:metabolism / Q000473:pathology
chemical_list: D002352:Carrier Proteins; D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human