Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China.
Department of Ophthalmology, University of Washington, Seattle, WA 98104, USA.
J Mater Chem B. 2022 Oct 5;10(38):7847-7861. doi: 10.1039/d2tb00114d.
Fungal keratitis (FK) is a refractory ophthalmic disease that can result in vision impairment and even blindness due to the severe fungal invasiveness and excessive inflammatory response. Therefore, antifungal treatment combined with local immunosuppressive therapy is regarded as the most effective strategy to improve the clinical outcome of FK. Oxidized polysaccharides with aldehyde groups possess obvious inhibitory activity towards microorganisms. Herein, we use chondroitin sulfate (CS), a recognized anti-inflammatory biopolysaccharide, to prepare oxidized chondroitin sulfate (OCS) sodium periodate (NaIO) oxidation for the treatment of FK. The chemical structure of OCS was characterized by FTIR, H NMR, and XPS, revealing that the -dihydroxy in the D-glucuronic acid unit of CS was selectively broken by NaIO, forming active aldehyde groups. The introduction of aldehydes not only retains the anti-inflammatory activity but also confers OCS with antifungal property. antifungal experiments showed that OCS inhibits the growth, represses the biofilm formation and alters the membrane integrity of . The toxicity of OCS was evaluated by cytotoxicity tests (CCK-8) and the Draize eye test and . qRT-PCR confirmed that OCS had similar anti-inflammatory activity as CS. In mice with keratitis, OCS CS or PBS showed an excellent therapeutic effect, characterized by a lower corneal inflammation score, less fungal load, reduced neutrophil recruitment, and the downregulated expression of pro-inflammatory factors. Our findings demonstrate that OCS improves the prognosis of keratitis in mice by inhibiting the growth of fungi, reducing the recruitment of neutrophils and inhibiting the inflammatory response. It provides innovative ideas for the development and application of OCS in medicine and biomaterials fields.
真菌性角膜炎（FK）是一种难治性眼部疾病，由于真菌的侵袭性强和过度炎症反应，可导致视力损害甚至失明。因此，抗真菌治疗联合局部免疫抑制治疗被认为是改善 FK 临床疗效的最有效策略。具有醛基的氧化多糖对微生物具有明显的抑制活性。在此，我们使用硫酸软骨素（CS），一种公认的抗炎生物多糖，通过 NaIO4 氧化制备氧化硫酸软骨素（OCS），用于 FK 的治疗。OCS 的化学结构通过傅里叶变换红外光谱（FTIR）、核磁共振氢谱（1H NMR）和 X 射线光电子能谱（XPS）进行了表征，结果表明 CS 中 D-葡萄糖醛酸单元的 -二羟基被 NaIO4 选择性地打破，形成活性醛基。醛基的引入不仅保留了抗炎活性，而且赋予 OCS 抗真菌性能。抗真菌实验表明，OCS 抑制 的生长，抑制生物膜形成并改变 的膜完整性。通过细胞毒性试验（CCK-8）和 Draize 眼试验以及 qRT-PCR 评估了 OCS 的毒性。结果表明，OCS 具有与 CS 相似的抗炎活性。在 性角膜炎小鼠模型中，OCS、CS 或 PBS 表现出优异的治疗效果，表现为角膜炎症评分较低、真菌负荷减少、中性粒细胞募集减少以及促炎因子的表达下调。我们的研究结果表明，OCS 通过抑制真菌的生长、减少中性粒细胞的募集和抑制炎症反应，改善了 性角膜炎小鼠的预后。这为 OCS 在医学和生物材料领域的开发和应用提供了创新思路。
