Abstract：
Dry eye affects majority of the global population, causing significant discomfort or even visual impairment, of which inflammation plays a crucial role in the deterioration process. This highlights the need for effective and safe anti-inflammatory treatments to achieve satisfactory therapeutic outcomes. This study focuses on the potential of tetrahedral framework nucleic acids (tFNA), a self-assembled nucleic acid material, as a simple and rapid treatment for oxidative stress and inflammation-induced disorders associated with dry eye. Mechanistically, tFNA is found to effectively alleviate dry eye damage by promoting corneal epithelial healing, restoring goblet cell function, and facilitating tear secretion recovery. Through RNA-seq analysis, it is observed that tFNA treatment normalizes the expression levels of most genes. Further exploration of the mechanism reveals that tFNA reduces excessive production of reactive oxygen species and modulates the inflammatory microenvironment, especially through cGAS-STING pathway thereby levels of inflammatory cytokines, including MMP9 and IL-6, are reduced. Additionally, tFNA demonstrates excellent safety performance without causing damage to the eye. Importantly, this study represents a successful application of nanophase materials with nucleic acid biological features for the effective treatment of dry eye, highlighting the potential clinical use of tFNA in the treatment of dry eye.
摘要：
干眼影响全球大多数人口，导致严重的不适甚至视力障碍，其中炎症在恶化过程中起着至关重要的作用。这突出了需要有效和安全的抗炎治疗以实现令人满意的治疗结果。本研究的重点是四面体框架核酸（tFNA）的潜力，自组装的核酸材料，作为一种简单而快速的治疗干眼症相关的氧化应激和炎症引起的疾病。机械上,发现tFNA通过促进角膜上皮愈合有效缓解干眼损伤，恢复杯状细胞功能，促进泪液分泌恢复。通过RNA-seq分析,观察到tFNA处理使大多数基因的表达水平正常化。机制的进一步探索表明，tFNA减少了活性氧的过度产生，并调节了炎症微环境，特别是通过cGAS-STING途径，从而提高炎症细胞因子的水平，包括MMP9和IL-6降低。此外,tFNA表现出优异的安全性能而不会对眼睛造成损害。重要的是,这项研究代表了具有核酸生物学特征的纳米材料在干眼症的有效治疗中的成功应用，强调tFNA在干眼治疗中的潜在临床应用。
