Circulating micronutrients as protective factors for the retinal structure and vasculature: Mendelian randomization analyses

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Advances in ophthalmology practice and research Pub Date : 2026-08-01 Epub Date: 2026-03-12 DOI:10.1016/j.aopr.2026.03.002

Linxin Wei, Meiqian He, Qing Zhao, Xinyu Zhao, Youxin Chen

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Abstract

Background

Epidemiological data and clinical trials have suggested that micronutrients may preserve retinal integrity by mitigating neurodegenerative alterations and microvascular damage. To strengthen the genetic evidence, we investigated the causal effects of various circulating micronutrients (CMs) on retinal imaging parameters using Mendelian randomization (MR) analyses.

Methods

Two-sample MR analyses utilized genetic variants as instrumental variables to investigate the effects of 14 CMs on retinal structural parameters including ganglion cell inner plexiform layer (GCIPL) thickness, outer nuclear layer thickness, and retinal nerve fiber layer thickness, as well as retinal vascular parameters comprising vascular density (VD) and fractal dimension (FD). Inverse variance weighted model was employed as the primary analytical method, with 5 sensitivity methods supplemented to confirm the results' robustness.

Results

Genetic predisposition to higher circulating folate levels was robustly associated with increased macular GCIPL thickness (β=0.94, 95% confidence interval (CI): 0.17–1.70, P=0.017), which remained significant (P=0.039) after MRlap correction. While nominal associations were observed between circulating vitamin B12 and vitamin E levels with both VD (vitamin B12: β=0.33, 95% CI: 0.09–0.56, P=0.007; vitamin E: β=0.19, 95% CI: 0.04–0.34, P=0.016) and FD (vitamin B12: β=0.24, 95% CI: 0.05−0.42, P=0.012; vitamin E: β=0.18, 95% CI: 0.04−0.33, P=0.016), these findings warranted a cautious interpretation due to inconsistencies across sensitivity analyses.

Conclusions

Our MR analyses evaluate the complex relationship between CMs and retinal imaging features, suggesting the protective and thus potentially therapeutic effects of folate in maintaining GCIPL thickness. Conversely, the potential associations observed for other micronutrients remain tentative and warrant cautious interpretation and further empirical validation.

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循环微量营养素作为视网膜结构和血管的保护因素：孟德尔随机化分析。

背景：流行病学数据和临床试验表明微量营养素可以通过减轻神经退行性改变和微血管损伤来保持视网膜完整性。为了加强遗传证据，我们使用孟德尔随机化（MR）分析研究了各种循环微量营养素（CMs）对视网膜成像参数的因果影响。方法：采用双样本MR分析，以遗传变异为工具变量，研究14 cm对神经节细胞内丛状层（GCIPL）厚度、外核层厚度、视网膜神经纤维层厚度等视网膜结构参数以及血管密度（VD）、分形维数（FD）等视网膜血管参数的影响。采用方差逆加权模型作为主要分析方法，辅以5种敏感性方法来验证结果的稳健性。结果：较高循环叶酸水平的遗传倾向与黄斑GCIPL厚度增加密切相关（β=0.94, 95%可信区间（CI）： 0.17-1.70， P=0.017），在MRlap校正后仍具有显著性（P=0.039）。虽然在VD（维生素B12: β=0.33, 95% CI: 0.09-0.56， P=0.007；维生素E: β=0.19, 95% CI: 0.04-0.34， P=0.016）和FD（维生素B12: β=0.24, 95% CI: 0.05-0.42， P=0.012；维生素E: β=0.18, 95% CI: 0.04-0.33， P=0.016）中观察到循环维生素B12和维生素E水平之间的名义关联，但由于敏感性分析的不一致性，这些发现需要谨慎解释。结论：我们的MR分析评估了CMs和视网膜成像特征之间的复杂关系，提示叶酸在维持GCIPL厚度方面具有保护和潜在的治疗作用。相反，观察到的其他微量营养素的潜在关联仍然是初步的，需要谨慎的解释和进一步的经验验证。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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