Association of plasma trace element levels with neovascular age-related macular degeneration

Heesterbeek, Thomas J.; Rouhi-Parkouhi, Mansour; Church, Stephanie J.; Lechanteur, Yara; Lorés‐Motta, Laura; Kouvatsos, Nikolaos; Clark, Simon J.; Bishop, Paul; Hoyng, Carel B.; Hollander, Anneke I. den; Unwin, Richard D.; Day, Anthony J.

doi:10.1016/j.exer.2020.108324

Cited by 14 publications

(7 citation statements)

References 72 publications

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“…The main biological consequences attributed to smoking is the increase in oxidative stress and inflammation in the retina and changes within the choroid, such as vasoconstriction and vessels branching [ 53 ]. The role of metal ions associated with smoking and their increased blood levels [ 54 ] and their accumulation in tissues has been implicated in AMD, and interestingly, smoking-related changes in the levels of metal ions associated with cigarette smoke are also positively associated with cataract formation [ 55 ].…”

Section: Risk Factors For Amdmentioning

confidence: 99%

The complement system in age-related macular degeneration

Armento

Ueffing

Clark

2021

Cell. Mol. Life Sci.

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165

128

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Age-related macular degeneration (AMD) is a chronic and progressive degenerative disease of the retina, which culminates in blindness and affects mainly the elderly population. AMD pathogenesis and pathophysiology are incredibly complex due to the structural and cellular complexity of the retina, and the variety of risk factors and molecular mechanisms that contribute to disease onset and progression. AMD is driven by a combination of genetic predisposition, natural ageing changes and lifestyle factors, such as smoking or nutritional intake. The mechanism by which these risk factors interact and converge towards AMD are not fully understood and therefore drug discovery is challenging, where no therapeutic attempt has been fully effective thus far. Genetic and molecular studies have identified the complement system as an important player in AMD. Indeed, many of the genetic risk variants cluster in genes of the alternative pathway of the complement system and complement activation products are elevated in AMD patients. Nevertheless, attempts in treating AMD via complement regulators have not yet been successful, suggesting a level of complexity that could not be predicted only from a genetic point of view. In this review, we will explore the role of complement system in AMD development and in the main molecular and cellular features of AMD, including complement activation itself, inflammation, ECM stability, energy metabolism and oxidative stress.

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Section: Risk Factors For Amdmentioning

confidence: 99%

The complement system in age-related macular degeneration

Armento

Ueffing

Clark

2021

Cell. Mol. Life Sci.

Self Cite

165

128

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“…On the other hand, Mg is the second most abundant intracellular cation involved in maintenance of cell membrane function, synthesis of nucleic acids, and energy metabolism. 96 Heesterbeek et al 97 determined by ICP-MS that Mg levels were higher in the plasma of AMD patients, but without statistical significance. Recently, Chang et al 98 reported that multiple dietary nutrients, including Mg, were associated with decreased risk for neovascular AMD.…”

Section: Discussionmentioning

confidence: 99%

Targeted Analysis of Tears Revealed Specific Altered Metal Homeostasis in Age-Related Macular Degeneration

Valencia

García

Fernández‐Vega

et al. 2022

Invest. Ophthalmol. Vis. Sci.

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Purpose Specific altered metal homeostasis has been investigated in the tear film of age-related macular degeneration (AMD) patients considering that metal dyshomeostasis contributes to the production of free radicals, inflammation, and apoptosis and results in conformational changes of proteins. Methods A multitargeted approach based on spectrophotometry and mass spectrometry techniques has been implemented to the multiplexed quantitation of lactoferrin (LF), S100 calcium binding protein A6 (S100A6), metallothionein 1A (MT1A), complement factor H (CFH), clusterin (CLU), amyloid precursor protein (APP), Mg, P, Na, Fe, Cu, Zn, and Ca, in the tear film from 60 subjects, 31 patients diagnosed with the dry form of AMD, and 29 healthy individuals Results Significant up-regulations of MT1A (1.9-fold) and S100A6 (1.4-fold) and down-regulations of LF (0.7-fold), Fe (0.6-fold), Mg (0.7-fold), and Cu (0.7-fold) were observed in AMD patients, when compared to control subjects. Of all the studied variables, only APP showed negative correlation with age in the AMD group. Also, positive correlations were observed for the variables Mg and Na, Cu and Mg, and P and Mg in both the AMD and control groups, whereas positive correlations were exclusively determined in the AMD group for Cu and LF, Na and Ca, and Mg and Ca. The panel constituted of MT1A, Na, and Mg predicts AMD disease in 73% of cases. Conclusions The different levels of target metals and (metallo-)proteins in the tear film suggest altered metal homeostasis in AMD patients. These observed pathophysiological changes may be related with the anomalous protein aggregation in the macula.

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“…In recent years, smoking and nutritional intake have been identified as important risk factors for AMD. The risk of AMD from smoking is dose-dependent, with a reduced risk of developing AMD after quitting, whereas smoking can increase the risk two to fourfold [28,29]. In terms of diet, a hyperglycemic diet is an important risk factor for AMD [30,31], whereas a "Mediterranean diet" rich in vitamins and carotenoids may reduce the risk of AMD [32][33][34].…”

Section: Amd As a Multifactorial Diseasementioning

confidence: 99%

Complement Inhibitors in Age-Related Macular Degeneration: A Potential Therapeutic Option

Qin

Dong

Yang

et al. 2021

Journal of Immunology Research

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Age-related macular degeneration (AMD) is a multifactorial disease, which can culminate in irreversible vision loss and blindness in elderly. Nowadays, there is a big gap between dry AMD and wet AMD on treatment. Accounting for nearly 90% of AMD, dry AMD still lacks effective treatment. Numerous genetic and molecular researches have confirmed the significant role of the complement system in the pathogenesis of AMD, leading to a deeper exploration of complement inhibitors in the treatment of AMD. To date, at least 14 different complement inhibitors have been or are being explored in AMD in almost 40 clinical trials. While most complement inhibitors fail to treat AMD successfully, two of them are effective in inhibiting the rate of GA progression in phase II clinical trials, and both of them successfully entered phase III trials. Furthermore, recently emerging complement gene therapy and combination therapy also offer new opportunities to treat AMD in the future. In this review, we aim to introduce genetic and molecular associations between the complement system and AMD, provide the updated progress in complement inhibitors in AMD on clinical trials, and discuss the challenges and prospects of complement therapeutic strategies in AMD.

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Association of plasma trace element levels with neovascular age-related macular degeneration

Cited by 14 publications

References 72 publications

The complement system in age-related macular degeneration

The complement system in age-related macular degeneration

Targeted Analysis of Tears Revealed Specific Altered Metal Homeostasis in Age-Related Macular Degeneration

Complement Inhibitors in Age-Related Macular Degeneration: A Potential Therapeutic Option

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