Jiang L, Wei R, Diao J, Ding H, Wang W, Ao R
Department of Ophthalmology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China.
Acta Endocrinol (Buchar). 2021 Jul-Sep;17(3):291-303. doi: 10.4183/aeb.2021.291.
Thyroid-associated ophthalmopathy (TAO), one of the most common orbital diseases in adults, seriously reduces patients' quality of life. Although human tear proteomics identified many abnormal expressed proteins and proposed several pathogeneses of TAO, most of these studies focused on the active stage or mixed types in TAO. In this study we identified significantly changed proteins and preliminary revealed the potential signalling pathways and mechanisms of TAO with the late, inactive stage.
Tears from TAO patients (n=6) with a CAS score < 3 and 6 control healthy subject were collected. The pooled tears were further fractionated using high pH reversed-phase chromatography, then submitted to LC-MS/MS and subsequent bioinformatic analysis.
Proteomic profiling identified 107 significantly changed proteins between the inactive stage of TAO patients and healthy cases. Among these proteins, 62 were upregulated, and 45 were downregulated in TAO cases compared to healthy individuals. Enrichment analysis revealed that the immune system, cell cycle, metabolism (carbohydrate metabolism and metabolism of cofactors and vitamins), protein synthesis and degradation might play a vital role in the progress of inactive TAO. The present investigation represents the first proteomic tear study of TAO patients in the inactive stage.
The results shed light on the differences between inactive TAO patients and healthy cases, thus enabling us to understand better the molecular mechanisms and potential targets for the treatment of inactive TAO.
甲状腺相关性眼病（TAO）是成人最常见的眼眶疾病之一，严重降低患者的生活质量。尽管人类泪液蛋白质组学鉴定出许多异常表达的蛋白质并提出了TAO的几种发病机制，但这些研究大多集中在TAO的活动期或混合型。在本研究中，我们鉴定了显著变化的蛋白质，并初步揭示了TAO晚期非活动期的潜在信号通路和机制。
收集6例临床活动评分（CAS）<3的TAO患者和6例健康对照者的泪液。将混合泪液进一步用高pH值反相色谱法分离，然后进行液相色谱-串联质谱分析及后续生物信息学分析。
蛋白质组分析确定了TAO患者非活动期与健康对照之间有107种显著变化的蛋白质。与健康个体相比，TAO患者中有62种蛋白质上调，45种蛋白质下调。富集分析显示，免疫系统、细胞周期、代谢（碳水化合物代谢以及辅因子和维生素代谢）、蛋白质合成和降解可能在非活动期TAO的进展中起重要作用。本研究是首次对非活动期TAO患者进行泪液蛋白质组学研究。
这些结果揭示了非活动期TAO患者与健康对照之间的差异，从而使我们能够更好地理解非活动期TAO的分子机制和潜在治疗靶点。
