Large-scale survey, animal models and computational modeling identify histological neurodegenerative biomarkers for traumatic optic neuropathy.

IF 6.3 1区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

JCI insight Pub Date : 2025-06-17 DOI:10.1172/jci.insight.190682

YiKui Zhang, BoYue Xu, ShiWei Huang, ZhaoHui Shi, Wei Xiong, Ruijun Wang, GuiQin Liu, Linlin Chen, ZhenHua Ge, YongJie Zhang, HongLei Liu, BaoYun Jia, Chunxia Wang, HaiHong Shi, Jun Kang, NingYu An, Shuirui Huang, De-Fu Chen, Shenghai Huang, YuTing Luo, MingYue Liu, ZhuoWei Wang, Zhonghao Yu, Jingwei Zheng, Wentao Yan, Gen Li, Hao Chen, XingGuang Deng, Shihui Wei, YunHai Tu, EnDe Wu, Kang Zhang, Wencan Wu

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引用次数: 0

Abstract

Background: Traumatic optic neuropathy (TON) is a leading cause of blindness following closed traumatic brain injury, with no effective treatments available. Previous interventional clinical trials were complicated by its low prevalence, variability in neurodegenerative severity, and unavailability of reliable biomarkers.

Methods: We analyzed data from 1226 patients enrolled in the prospective National Multi-Center Collaborative Clinical Research Program of China (2017-2024) to establish a clinical profile and identify non-invasive biomarkers for neurodegenerative severity. Subgroup analysis of monocular TON patients revealed potential biomarkers including visual functional parameters, inner retinal thickness, and time post-injury.

Results: The ganglion cell complex (GCC) thickness showed a strong correlation with retinal ganglion cell somata (R² = 0.87, p < .0001) and axon density (R² = 0.89, p < .0001) in a clinically relevant large animal model. Computational analysis demonstrated that using GCC thickness as a biomarker could substantially enhance the statistical power of clinical trials (by up to 4.5-fold), as confirmed by real-world data.

Conclusion: This study presented the largest epidemiological analysis of TON to date and established GCC thickness as a crucial biomarker for stratifying disease severity and improving the efficiency of clinical trials.

Trial registration: Chinese Clinical Trial Registry (ChiCTR-OOC-17013437).

Funding: National Key R&D Program of China (Grant No.2022YFA1105500); Key Science and Technology Program of Wenzhou (Grant No.ZY2022021); National Natural Science Foundation of China (Grant No.82471080).

查看原文本刊更多论文

大规模调查，动物模型和计算模型确定创伤性视神经病变的组织学神经退行性生物标志物。

背景：外伤性视神经病变（TON）是闭合性创伤性脑损伤后致盲的主要原因，目前尚无有效的治疗方法。先前的干预性临床试验因其低患病率、神经退行性严重程度的可变性以及缺乏可靠的生物标志物而变得复杂。方法：我们分析了中国前瞻性国家多中心协同临床研究计划（2017-2024）的1226例患者的数据，以建立临床资料并确定神经退行性严重程度的非侵入性生物标志物。单眼TON患者的亚组分析揭示了潜在的生物标志物，包括视觉功能参数、视网膜内厚度和损伤后时间。结果：在临床相关的大型动物模型中，神经节细胞复合体（GCC）厚度与视网膜神经节细胞体（R²= 0.87,p < 0.0001）和轴突密度（R²= 0.89,p < 0.0001）有很强的相关性。计算分析表明，使用GCC厚度作为生物标志物可以大大提高临床试验的统计能力（高达4.5倍），这得到了实际数据的证实。结论：本研究提出了迄今为止最大规模的TON流行病学分析，并确立了GCC厚度作为疾病严重程度分层和提高临床试验效率的关键生物标志物。试验注册：中国临床试验注册中心（ChiCTR-OOC-17013437）。国家重点科技发展计划（批准号：2022yfa1105500）；温州市科技重点计划（批准号：zy2022021）；国家自然科学基金（资助号：82471080）。

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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来源期刊

JCI insight Medicine-General Medicine

CiteScore

13.70

自引率

1.20%

发文量

543

审稿时长

6 weeks

期刊介绍： JCI Insight is a Gold Open Access journal with a 2022 Impact Factor of 8.0. It publishes high-quality studies in various biomedical specialties, such as autoimmunity, gastroenterology, immunology, metabolism, nephrology, neuroscience, oncology, pulmonology, and vascular biology. The journal focuses on clinically relevant basic and translational research that contributes to the understanding of disease biology and treatment. JCI Insight is self-published by the American Society for Clinical Investigation (ASCI), a nonprofit honor organization of physician-scientists founded in 1908, and it helps fulfill the ASCI's mission to advance medical science through the publication of clinically relevant research reports.