Age-Related Macular Degeneration in the Aspect of Chronic Low-Grade Inflammation (Pathophysiological ParaInflammation)

Abstract

The products of oxidative stress trigger chronic low-grade inflammation (pathophysiological parainflammation) process in AMD patients. In early AMD, soft drusen contain many mediators of chronic low-grade inflammation such as C-reactive protein, adducts of the carboxyethylpyrrole protein, immunoglobulins, and acute phase molecules, as well as the complement-related proteins C3a, C5a, C5, C5b-9, CFH, CD35, and CD46. The complement system, mainly alternative pathway, mediates chronic autologous pathophysiological parainflammation in dry and exudative AMD, especially in the Y402H gene polymorphism, which causes hypofunction/lack of the protective complement factor H (CFH) and facilitates chronic inflammation mediated by C-reactive protein (CRP). Microglial activation induces photoreceptor cells injury and leads to the development of dry AMD. Many autoantibodies (antibodies against alpha beta crystallin, alpha-actinin, amyloid, C1q, chondroitin, collagen I, collagen III, collagen IV, elastin, fibronectin, heparan sulfate, histone H2A, histone H2B, hyaluronic acid, laminin, proteoglycan, vimentin, vitronectin, and aldolase C and pyruvate kinase M2) and overexpression of Fcc receptors play role in immune-mediated inflammation in AMD patients and in animal model. Macrophages infiltration of retinal/choroidal interface acts as protective factor in early AMD (M2 phenotype macrophages); however it acts as proinflammatory and proangiogenic factor in advanced AMD (M1 and M2 phenotype macrophages).

P2Y1 Receptor Signaling Contributes to High Salt-Induced Priming of the NLRP3 Inflammasome in Retinal Pigment Epithelial Cells

“…Chronic innate immune activation contributes to the dysfunction and progressive degeneration of the RPE underlying AMD [2, 4]. Activation of the NLRP3 inflammasome was implicated in mediating the degeneration of the RPE in geographic atrophy [8, 9], the late stage of dry AMD, and the development of choroidal neovascularization [7, 10], the hallmark of neovascular AMD.…”

“…The remaining patients suffer from the neovascular form characterized by choroidal neovascularization. AMD is associated with systemic and local inflammation [2–4]. Generally, inflammatory processes are activated by cytosolic protein-signaling complexes, termed inflammasomes.…”

Can innate and autoimmune reactivity forecast early and advance stages of age-related macular degeneration?

“…For example, AAbs to elastin, heparan sulfate, fibronectin, histone H2B, collagen III, and collagen IV were significantly elevated in sera of AMD patients compared to normal controls [56]. Another study identified more autoantigens, including αβ-crystallin, α-actinin, amyloid, C1q protein, chondroitin, collagen I, III, and IV, elastin, histone H2A and H2B, laminin, vimentin, vitronectin, aldolase C, and pyruvate kinase M2 [16]. AAbs against cyclic nucleotide phosphodiesterase, phosphatidylserine (PS), and proliferating cell nuclear antigen [56], glial fibrillary acidic protein (GFAP), and α-enolase were also documented.…”

Dietary fatty acids and lipoproteins on progression of age-related macular degeneration

“…high intake of cholesterol and dietary fats or low intake of dietary vitamin D, zinc, and antioxidants) may also play a role in the pathogenesis of AMD (Clemons et al, 2005;Dasari et al, 2011;Millen et al, 2015;Parekh et al, 2009;Sui et al, 2013). Furthermore, AMD has been recently associated with retinal low-grade inflammation linked by the infiltration and activation of immune cells and production of inflammatory mediators into the site of retinal damage (Nita et al, 2014;Whitcup et al, 2013).…”