Age-Related Macular Degeneration: Role of Oxidative Stress and Blood Vessels

Abstract

Age-related macular degeneration (AMD) is a common irreversible ocular disease characterized by vision impairment among older people. Many risk factors are related to AMD and interact with each other in its pathogenesis. Notably, oxidative stress and choroidal vascular dysfunction were suggested to be critically involved in AMD pathogenesis. In this review, we give an overview on the factors contributing to the pathophysiology of this multifactorial disease and discuss the role of reactive oxygen species and vascular function in more detail. Moreover, we give an overview on therapeutic strategies for patients suffering from AMD.

Keywords: age-related macular degeneration; choroidal vascular dysfunction; dysregulated lipid metabolism; genetic factor; oxidative stress; pathogenesis.

Figure 1

Anatomy of the fundus and macula. Abbreviations: RPE: retinal pigment epithelium; BM: Bruch’s membrane.

Figure 2

Clinical manifestation and pathology of AMD from the early to late stage. Medium-sized drusen found in early AMD. Intermediate AMD shows the presence of large drusen. Late AMD is classified into GA and neovascular AMD. GA is defined by the deterioration of the RPE, photoreceptor layer, and choroidal capillaries in the macula. The invasion of abnormal fragile choroidal blood vessels growing from the choroid into the retina in neovascular AMD, with blood and fluid leakage. Abbreviations: AMD: age-related macular degeneration; GA: geographic atrophy.

Figure 3

The interplay between ROS and CNV formation. Abbreviations: CNV: choroidal neovascularization; ROS: reactive oxygen species; mtROS: mitochondrial ROS; NOX: nicotinamide adenine dinucleotide phosphate oxidase; LOX: lysyl oxidase; eNOS: endothelial nitric oxide synthases; ONOO⁻: peroxynitrite; MAPKs: mitogen-activated protein kinases; NF-κB: nuclear factor-κB; VEGF: vascular endothelial growth factor; VEGFR2: vascular endothelial growth factor receptor 2; ERK: extracellular signal-regulated kinase; PI-3K: phosphoinositol 3-kinase; AP-1: activator protein 1; NLRP3: nod-like receptor family pyrin domain containing 3; TNF: tumor necrosis factor; IL-1β: interleukin-1β; IL-18: interleukin-18; HIF-1: hypoxia-inducible factor 1; ICAM-1: intercellular adhesion molecule-1.