Mechanism of Inflammation in Age-Related Macular Degeneration

Abstract

Age-related macular degeneration (AMD) is a multifactorial disease that represents the most common cause of irreversible visual impairment among people over the age of 50 in Europe, the United States, and Australia, accounting for up to 50% of all cases of central blindness. Risk factors of AMD are heterogeneous, mainly including increasing age and different genetic predispositions, together with several environmental/epigenetic factors, that is, cigarette smoking, dietary habits, and phototoxic exposure. In the aging retina, free radicals and oxidized lipoproteins are considered to be major causes of tissue stress resulting in local triggers for parainflammation, a chronic status which contributes to initiation and/or progression of many human neurodegenerative diseases such as AMD. Experimental and clinical evidences strongly indicate the pathogenetic role of immunologic processes in AMD occurrence, consisting of production of inflammatory related molecules, recruitment of macrophages, complement activation, microglial activation and accumulation within those structures that compose an essential area of the retina known as macula lutea. This paper reviews some attractive aspects of the literature about the mechanisms of inflammation in AMD, especially focusing on those findings or arguments more directly translatable to improve the clinical management of patients with AMD and to prevent the severe vision loss caused by this disease.

Subretinal injection of amyloid-β peptide accelerates RPE cell senescence and retinal degeneration

“…AMD is an age-related chronic inflammatory disease (50,51). Our previous study (19) and the present study indicate that Aβ-induced senescent RPE cells may constitute a link between chronic inflammation and neuroretinal degeneration.…”

Lutein supplementation leads to decreased soluble complement membrane attack complex sC5b‐9 plasma levels

“…The molecular mechanisms causing AMD remain unknown although inflammatory processes have been implicated as evidenced by the identification of susceptibility genes encoding complement factors (Tuo et al 2004;Klein et al 2005;Chen et al 2010;Khandhadia et al 2012) and the presence of complement proteins in drusen (Hageman et al 2001). These findings were supported by studies showing an increase in the level of various complement activation products in the circulation of AMD patients (Donoso et al 2006;Scholl et al 2008;Reynolds et al 2009;Hecker et al 2010) and provided further evidence for a systemic inflammatory component to the disease pathogenesis (Parmeggiani et al 2012). The exact relationship between AMD and the innate immune system, however, remains to be clarified.…”

NETWORK APPROACH TO ANALYSIS OF QUANTITATIVE TRAIT LOCI FOR TUMOR NECROSIS FACTOR (TNFα-863, TNFα-308, TNFα-238), VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF-2578, VEGF+936) AND MATRIX METALLOPROTEINASE (Ммр2-1306, Ммр3-1171, Ммр9-1569) GENES IN AGERELATED MACULAR DEGENERATION

“…Возрастная макулярная дегенерация (ВМД) -одно из самых распространенных мультифактори-альных заболеваний глаз, являющееся основной причиной необратимого ухудшения центрально-го зрения в пожилом возрасте [28]. Атрофическая (сухая) форма ВМД может переходить в более тя-желую экссудативную (влажную) форму, которая часто является причиной слепоты.…”

“…Для этого типа ВМД характерно формирование хориоидальной неоваскулярной мембраны (ХНВМ), которая образована патологическими кровеносными со-судами, врастающими в слои сетчатки из сосуди-стой оболочки [8]. Факторы риска ВМД гетероген-ны: ключевыми являются возраст, генетические факторы предрасположенности к заболеванию, целый ряд эпигенетических факторов [28]. Фак-тор роста эндотелия сосудов (VEGF) -важный фактор ангиогенеза, а повышенные концентра- 2017, Vol.…”