MicroRNA expression profiling in tears and blood as predictive biomarkers for anti-VEGF treatment response in wet age-related macular degeneration

Graefe's Archive for Clinical and Experimental Ophthalmology Pub Date : 2024-04-06 DOI:10.1007/s00417-024-06478-x

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Abstract

Purpose

This study aimed to investigate the potential of microRNAs (miRNAs) in tears, blood, and aqueous humor as biomarkers for predicting treatment response in wet age-related macular degeneration (AMD) patients undergoing anti-vascular endothelial growth factor (anti-VEGF) therapy.

Methods

In a single-center prospective cohort study, treatment-naïve wet AMD patients and age-matched controls were enrolled. Clinical data and miRNA levels (miR-199a-3p, miR-365-3p, miR-200b-3p, miR-195-5p, miR-335-5p, and miR-185-5p) in tears, blood, and aqueous humor were collected. Treatment response was categorized into responders and non-responders based on visual acuity and central subfield thickness. MiRNA levels were quantified using reverse-transcription PCR. Statistical analyses were performed, including ROC analysis, to evaluate predictive accuracy.

Results

Dysregulated miRNA profiles were observed in wet AMD tears and blood compared to controls. Specifically, miR-199a-3p, miR-195-5p, and miR-185-5p were upregulated, while miR-200b-3p was downregulated in tears. All six miRNAs were elevated in wet AMD blood samples. Notably, responders showed higher tear expression of miR-195-5p and miR-185-5p. Combining these miRNAs yielded the highest predictive power (AUC = 0.878, p = 0.006) for anti-VEGF responders.

Conclusions

Dysregulated miRNA profiles in tears and blood suggest their potential as biomarkers for wet AMD. MiR-195-5p and miR-185-5p in tears demonstrate predictive value for anti-VEGF treatment responders. This study underscores the non-invasive prediction potential of miRNA tear analysis in wet AMD treatment responses.

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泪液和血液中的微RNA表达谱分析是湿性老年性黄斑变性患者抗血管内皮生长因子治疗反应的预测性生物标志物

摘要目的本研究旨在探讨泪液、血液和房水中的微RNA（miRNA）作为生物标志物的潜力，以预测接受抗血管内皮生长因子（anti-VEGF）治疗的湿性年龄相关性黄斑变性（AMD）患者的治疗反应。方法在一项单中心前瞻性队列研究中，招募了治疗无效的湿性 AMD 患者和年龄匹配的对照组。研究人员收集了临床数据以及泪液、血液和房水中的 miRNA 水平（miR-199a-3p、miR-365-3p、miR-200b-3p、miR-195-5p、miR-335-5p 和 miR-185-5p）。根据视力和中央子场厚度将治疗反应分为有反应者和无反应者。使用反转录 PCR 对 MiRNA 水平进行量化。进行统计分析，包括 ROC 分析，以评估预测的准确性。结果与对照组相比，在湿性 AMD 泪液和血液中观察到了失调的 miRNA 图谱。具体来说，泪液中的 miR-199a-3p、miR-195-5p 和 miR-185-5p 上调，而 miR-200b-3p 下调。所有六种 miRNA 在湿性 AMD 血液样本中都升高了。值得注意的是，应答者的泪液中 miR-195-5p 和 miR-185-5p 表达较高。将这些 miRNA 结合起来，对抗 VEGF 反应者的预测能力最高（AUC = 0.878，p = 0.006）。结论泪液和血液中失调的 miRNA 图谱表明它们有可能成为湿性 AMD 的生物标记物。泪液中的 miR-195-5p 和 miR-185-5p 对抗 VEGF 治疗应答者具有预测价值。这项研究强调了泪液中 miRNA 分析在湿性 AMD 治疗反应中的非侵入性预测潜力。

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Graefe's Archive for Clinical and Experimental Ophthalmology

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