Although the triggers causing angiogenesis in the context of neovascular age-related macular degeneration (nAMD) are not fully understood, oxidative stress is likely involved. Oxidative stress in the eye can occur through exposure of macular tissues to sunlight and local or systemic exposure to oxidative stressors associated with environmental or lifestyle factors. Because trace elements have been implicated as regulators of oxidative stress and cellular antioxidant defense mechanisms, we hypothesized that they may play a role as a risk factor, modifying the progression toward nAMD.

Herein, we determined whether levels of human plasma trace elements are different in 236 individuals with nAMD compared to 236 age-matched controls without AMD. Plasma levels of 16 trace elements including arsenic, barium, calcium, cadmium, cobalt, chromium, copper, iron, magnesium, manganese, molybdenum, lead, antimony, selenium, vanadium and zinc were measured using inductively coupled plasma mass spectrometry. Associations of trace elements with demographic, environmental and lifestyle factors and AMD-associated genetic variants were assessed.

Elevated levels of barium and cadmium and reduced levels of chromium were observed in nAMD patients compared to controls. Mean plasma concentrations of barium were 1.35 μg/L (standard deviation [SD] 0.71) in nAMD and 1.15 μg/L (SD 0.63) in controls (P = 0.001). Mean levels of chromium were 0.37 μg/L (SD 0.22) in nAMD and 0.46 μg/L (SD 0.34) in controls (P = 0.001). Median levels for cadmium, which were not normally distributed, were 0.016 μg/L (interquartile range [IQR] 0.001–0.026) in nAMD and 0.012 μg/L (IQR 0.001–0.022) in controls (P = 0.002). Comparison of the Spearman's correlation coefficients between nAMD patients and controls identified a difference in correlations for 8 trace elements. Cadmium levels were associated with the smoking status (P < 0.001), while barium levels showed a trend of association with the usage of antihypertensive drugs. None of the AMD-associated genetic variants were associated with any trace element levels.

In conclusion, in this case-control study we detected elevated plasma levels of barium and cadmium and reduced plasma levels of chromium in nAMD patients. An imbalance in plasma trace elements, which is most likely driven by environmental and lifestyle factors, might have a role in the pathogenesis of AMD. These trace elements may be incorporated as biomarkers into models for prediction of disease risk and progression. Additionally, population-based preventive strategies to decrease Cd exposure, especially by the cessation of smoking, could potentially reduce the burden of nAMD. Future studies are warranted to investigate whether supplementation of Cr would have a beneficial effect on nAMD.

尽管新生血管性年龄相关性黄斑变性 (nAMD) 背景下引起血管生成的触发因素尚不完全清楚，但氧化应激可能参与其中。眼睛中的氧化应激可通过黄斑组织暴露于阳光以及局部或全身暴露于与环境或生活方式因素相关的氧化应激源而发生。由于微量元素被认为是氧化应激和细胞抗氧化防御机制的调节剂，我们假设它们可能作为危险因素发挥作用，改变 nAMD 的进展。

在此，我们确定了 236 名 nAMD 患者与 236 名年龄匹配的非 AMD 对照者的血浆微量元素水平是否存在差异。采用电感耦合等离子体质谱法测量砷、钡、钙、镉、钴、铬、铜、铁、镁、锰、钼、铅、锑、硒、钒和锌等 16 种微量元素的血浆水平。评估了微量元素与人口、环境和生活方式因素以及 AMD 相关遗传变异的关联。

与对照组相比，nAMD 患者的钡和镉水平升高，铬水平降低。nAMD 中钡的平均血浆浓度为 1.35 μg/L（标准差 [SD] 0.71），对照组为 1.15 μg/L（SD 0.63）（P = 0.001）。nAMD 中铬的平均水平为 0.37 μg/L (SD 0.22)，对照组为 0.46 μg/L (SD 0.34)（P = 0.001）。镉的中位水平不呈正态分布，nAMD 中镉的中位水平为 0.016 μg/L（四分位距 [IQR] 0.001-0.026），对照组为 0.012 μg/L（IQR 0.001-0.022）（P = 0.002）。比较 nAMD 患者和对照组之间的 Spearman 相关系数，发现 8 种微量元素的相关性存在差异。镉水平与吸烟状况相关（P < 0.001），而钡水平则显示出与抗高血压药物的使用相关的趋势。AMD 相关的遗传变异均与任何微量元素水平无关。

总之，在这项病例对照研究中，我们检测到 nAMD 患者血浆中钡和镉水平升高，而血浆铬水平降低。血浆微量元素失衡很可能是由环境和生活方式因素引起的，可能在 AMD 的发病机制中发挥作用。这些微量元素可以作为生物标志物纳入预测疾病风险和进展的模型中。此外，基于人群的减少镉暴露的预防策略，特别是通过戒烟，可能会减轻 nAMD 的负担。未来的研究有必要调查补充 Cr 是否会对 nAMD 产生有益影响。