The role of NAD+ metabolism in macrophages in age-related macular degeneration. (January 2023)

• Record Type: Journal Article
• Authors: Lin, Ruoyi; Yu, Jing
• Is Part Of: Mechanisms of ageing and development. Volume 209(2023)
• Publication Date: 2023-01
• Subjects: AMD age-related macular degeneration -- CI confidence interval -- MSVI moderate and severe vision impairment -- RPE retinal pigment epithelium -- BrM Bruch's membrane -- nAMD neovascular AMD -- GA geographic atrophy -- BRB blood-retina barrier -- Mφs macrophages -- SASPs senescence-associated secretory phenotypes -- NAD+ nicotinamide adenine dinucleotide -- NA nicotinic acid -- NMN nicotinamide mononucleotide -- NAM nicotinamide -- ADPR adenosine diphosphoribose -- NAMPT nicotinamide phosphoribosyltransferase -- SIRT sirtuin -- PARPs poly(ADP- ribose) polymerases -- LPS lipopolysaccharide -- NF-κB nuclear factor-kappa B -- TNF tumor necrosis factor -- IL interleukin -- iNOS inducible nitric oxide synthase -- ROI reactive oxygen intermediates -- ROS reactive oxygen species -- M-CSF macrophage colony stimulating factor -- IPM interphotoreceptor matrix -- CEP carboxyethylpyrrole -- CNV choroidal neovascularization -- I/R ischemia/reperfusion -- RP retinitis pigmentosa -- VEGF vascular endothelial growth factor; Age-related macular degeneration -- NAD+ metabolism -- Macrophages -- M1 macrophages; Aging -- Periodicals; Developmental biology -- Periodicals; Aging -- Periodicals; Developmental Biology -- Periodicals; Vieillissement -- Périodiques; Biologie du développement -- Périodiques; Aging; Developmental biology; Periodicals; 612.67
• DOI: 10.1016/j.mad.2022.111755
• Languages: English
• ISSNs: 0047-6374

Abstract

Abstract: Age-related macular degeneration (AMD) is a leading cause of legal blindness and moderate and severe vision impairment (MSVI) in people older than 50 years. It is classified in various stages including early, intermediate, and late stage. In the early stages, innate immune system, especially macrophages, play an essential part in disease onset and progression. NAD + is an essential coenzyme involved in cellular senescence and immune cell function, and its role in age-related diseases is gaining increasing attention. The imbalance between the NAD + synthesis and consumption causes the fluctuation of intracellular NAD + level which determines the polarization fate of macrophages. In AMD, the over-expression of NAD + -consuming enzymes in macrophages leads to declining of NAD + concentrations in the microenvironment. This phenomenon triggers the activation of inflammatory pathways in macrophages, positive feedback aggregation of inflammatory cells and accumulation of reactive oxygen species (ROS). This review details the role of NAD + metabolism in macrophages and molecular mechanisms during AMD. The selected pathways were identified as potential targets for intervention in AMD, pending further investigation. Highlights: The intracellular and interstitial NAD + levels decrease during age-related macular degeneration. M1 macrophage polarization characterized by decreased intracellular NAD + levels and overexpression of CD38, and M2 macrophage polarization characterized by increased intracellular NAD + levels and activation of NAMPT. M1 macrophage infiltration is associated with the onset of AMD, early AMD and geographic atrophy (GA), and M2 macrophage infiltration is associated with neovascular AMD (nAMD). Overexpression and activation of CD38 in M1 macrophages decreases intracellular NAD+ levels in the early AMD stages.