关键词: DNA methylation blood−retina barrier graphene quantum dots retinal degeneration surface modification

Mesh : Quantum Dots / chemistry toxicity Graphite / chemistry Animals DNA Methylation Retinal Degeneration Blood-Retinal Barrier / metabolism Zebrafish

来  源:   DOI:10.1021/acs.est.4c02179

Abstract:
Graphene quantum dots (GQDs) are used in diverse fields from chemistry-related materials to biomedicines, thus causing their substantial release into the environment. Appropriate visual function is crucial for facilitating the decision-making process within the nervous system. Given the direct interaction of eyes with the environment and even nanoparticles, herein, GQDs, sulfonic acid-doped GQDs (S-GQDs), and amino-functionalized GQDs (A-GQDs) were employed to understand the potential optic neurotoxicity disruption mechanism by GQDs. The negatively charged GQDs and S-GQDs disturbed the response to light stimulation and impaired the structure of the retinal nuclear layer of zebrafish larvae, causing vision disorder and retinal degeneration. Albeit with sublethal concentrations, a considerably reduced expression of the retinal vascular sprouting factor sirt1 through increased DNA methylation damaged the blood-retina barrier. Importantly, the regulatory effect on vision function was influenced by negatively charged GQDs and S-GQDs but not positively charged A-GQDs. Moreover, cluster analysis and computational simulation studies indicated that binding affinities between GQDs and the DNMT1-ligand binding might be the dominant determinant of the vision function response. The previously unknown pathway of blood-retinal barrier interference offers opportunities to investigate the biological consequences of GQD-based nanomaterials, guiding innovation in the industry toward environmental sustainability.
摘要:
石墨烯量子点(GQD)用于从化学相关材料到生物医学的各个领域,从而导致它们大量释放到环境中。适当的视觉功能对于促进神经系统内的决策过程至关重要。考虑到眼睛与环境甚至纳米粒子的直接相互作用,在这里,GQD,磺酸掺杂的GQDs(S-GQDs),和氨基功能化的GQDs(A-GQDs)用于了解GQDs潜在的视神经毒性破坏机制。带负电荷的GQDs和S-GQDs干扰了斑马鱼幼虫对光刺激的反应并损害了视网膜核层的结构,导致视力障碍和视网膜变性.尽管具有亚致死浓度,通过增加DNA甲基化,视网膜血管发芽因子sirt1的表达显着降低,从而破坏了血-视网膜屏障。重要的是,对视觉功能的调节作用受到带负电荷的GQDs和S-GQDs的影响,但不受带正电荷的A-GQDs的影响。此外,聚类分析和计算模拟研究表明,GQDs与DNMT1-配体结合之间的结合亲和力可能是视觉功能反应的主要决定因素。先前未知的血液-视网膜屏障干扰途径为研究基于GQD的纳米材料的生物学后果提供了机会。引导行业创新走向环境可持续性。
公众号