Gao Shunxiang, Guo Dongling, Huang Peirong, Yin Ning, Jia Huixun, Li Shengjie, Sun Xiaodong, Zhu Xiangjia
Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China.
National Clinical Research Center for Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, 200080, China.
J Nanobiotechnology. 2025 Aug 14;23(1):565. doi: 10.1186/s12951-025-03627-0.
Accurate, sensitive, and specific detection of molecular markers in intraocular fluid will facilitate the early discovery, diagnosis, and intervention of eye diseases. In this study, a total of 168 participants were recruited and divided into two distinct cohorts: discovery and verification. In the discovery phase, proteomic analysis identified MCP-1 in aqueous humor as a potential molecular marker for blinding eye disease. We further developed a molecular detection technology for the marker based on biolayer interference sensing. The technology utilizes a sandwich strategy with one-to-one pairing of two different biorecognition molecules for MCP-1. It also incorporates automation, high throughput, and real-time monitoring, achieving highly selective recognition and accurate analysis of MCP-1. It demonstrates a low detection limit (0.16 pM), good reliability (R = 0.995), and a wide analytical range (0.244-1000 pM) for MCP-1 in human aqueous humor samples. Crucially, in the verification phase with 150 subjects, the technology achieved a high detection rate (95.0%) for patients with age-related macular degeneration and high myopia cataract in under 30 min, and was able to further differentiate between them with a specificity of 86.0%. Therefore, the developed molecular detection technology may provide a robust, convenient, and valuable solution for widespread screening, early discovery, and differential diagnosis of blinding eye diseases.
准确、灵敏且特异的眼内液分子标志物检测将有助于眼部疾病的早期发现、诊断和干预。在本研究中,共招募了168名参与者,并将其分为两个不同的队列:发现队列和验证队列。在发现阶段,蛋白质组学分析确定房水中的单核细胞趋化蛋白-1(MCP-1)为致盲性眼病的潜在分子标志物。我们进一步基于生物层干涉传感技术开发了针对该标志物的分子检测技术。该技术采用夹心策略,使用两种不同的生物识别分子与MCP-1进行一对一配对。它还具备自动化、高通量和实时监测功能,实现了对MCP-1的高选择性识别和准确分析。在人房水样本中,它对MCP-1的检测限低(0.16 pM)、可靠性好(R = 0.995)且分析范围广(0.244 - 1000 pM)。至关重要的是,在对150名受试者的验证阶段,该技术在30分钟内对年龄相关性黄斑变性和高度近视性白内障患者的检测率高达95.0%,并且能够以86.0%的特异性进一步区分这两种疾病。因此,所开发的分子检测技术可能为致盲性眼病的广泛筛查、早期发现和鉴别诊断提供一种强大、便捷且有价值的解决方案。