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导航360°Schlemm管手术的新型荧光纤维构建及其临床前关键实验研究

批准号:
82101122
项目类别:
青年科学基金项目(C类)
资助金额:
30.0 万元
负责人:
梁亚
依托单位:
学科分类:
青光眼、视神经及视路疾病
结题年份:
2024
批准年份:
2021
项目状态:
已结题
项目参与者:
梁亚

项目摘要

结项摘要

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中文摘要
青光眼是全球第一位不可逆性致盲性眼病。目前治疗青光眼最前沿、最有效的方法之一是360°Schlemm管手术,其关键和难点为穿过全周Schlemm管,但缺乏简便、易普及的穿管方法。我们研究发现,负载有量子点的海藻酸钠水凝胶荧光纤维与聚丙烯缝线的力学性能类似,可穿过部分Schlemm管并透过巩膜可视。基于此,本项目拟制备可通过手术显微镜自身光源激发发出红光、“可视化”导航穿过全周Schlemm管的新型功能化荧光纤维。通过建立兼具手术导航及活体成像功能的荧光纤维的可控制备方法,制备修饰有光切荧光探针的荧光纤维并优化其性能;在细胞和动物层面,通过PCR、免疫组化等方法,系统研究荧光纤维的手术导航及活体成像效果;阐明材料性能与手术效果的内在联系,利用活体成像技术探讨发病机制。本项目旨在为新型荧光纤维的临床转化奠定理论和实验基础,为360°Schlemm管手术及青光眼的发病机制研究提供新思路。
英文摘要
Glaucoma is the first leading reason for irreversible blindness in the world. At present, one of the most advanced and effective treatments for glaucoma is 360-degree Schlemm’s canal surgery. The key and difficulty of the surgery are to pass through the whole Schlemm’s canal. But there is a lack of simple and popular methods. We found that the fluorescent fiber of sodium alginate hydrogel loaded with quantum dots exhibited mechanical properties similar to those of polypropylene sutures. The fiber passed through part of the Schlemm’s canal and could be seen through the sclera. Therefore, this project is designed to prepare a novel functionalized fluorescent fiber that can emit red light by the light of the operating microscope itself, and visually guide the canalization of the whole Schlemm’s canal. By establishing a controllable method for the preparation of a fluorescent fiber with both surgical navigation and in vivo imaging functions, a fluorescent fiber modified with light-sectioning fluorescent probes is prepared and their properties are optimized. At the cell and animal levels, the surgical navigation and in vivo imaging effects of the fluorescent fiber are systematically studied by PCR, immunohistochemistry, and other methods. This project aims to elucidate the internal relationship between material properties and surgical results and to explore the pathogenesis by using in vivo imaging technology. This project aims to lay the theoretical and experimental foundation for the clinical transformation of the novel fluorescent fiber and provide a new idea for 360-degree Schlemm's canal surgery and the pathogenesis of glaucoma.
青光眼是全球第一位不可逆性致盲性眼病,治疗青光眼最前沿、最有效的方法之一是360° Schlemm管手术,其关键和难点为穿过全周直径仅约300微米的Schlemm管。但是,360° Schlemm管手术缺乏简便、易普及的穿管方法。为突破这一瓶颈,本项目立足临床需求,结合前沿纳米技术,开发并优化由光源激发发出红光、“可视化”导航穿过全周Schlemm管的新型荧光纤维;在细胞和动物层面,应用PCR、免疫组化等方法,探讨新型荧光纤维的手术导航效果及安全性。在细胞水平,通过培养小梁细胞,与荧光纳米纤维作用,证明了新型荧光纤维对细胞的周期、增殖及凋亡均没有影响。在动物实验中,证实新型荧光纤维导航穿过全周Schlemm管的成功率与发光微导管相似,且与新型荧光纤维接触的组织病理显示未见明显炎症浸润和血管增生。目前在申请专利。同时,制备了与兔小梁网尺寸相匹配的金属框架颗粒,前房注入构建兔高眼压模型,并前房注入吲哚菁绿,进行房水造影,以实现精准定位房水阻力部位。此外,采用谱域光学相干断层成像扫描并对比缝线导航的360°Schlemm管成形术前及术后Schlemm管腔大小,以探索360°Schlemm管手术降低眼压的机制。该研究提供了一种评价360°Schlemm管扩张手术前后Schlemm管腔形态学改变的方法,证明了Schlemm管的扩张越显著,眼压下降越明显;且患者青光眼的病情越轻,降低眼压的效果越好。本项目的研究将为360° Schlemm手术穿管材料的选择提供实验基础和理论依据,为荧光纤维的后续临床转化奠定实验基础,为360° Schlemm管手术的发展及青光眼发病机制的研究提供新思路,新型荧光纤维具有中国自主知识产权,具有转化前景。还为构建动物高眼压模型提供了新的思路。为360°Schlemm管扩张术效果的客观评价和临床效果预测提供了循证依据,具有良好的临床应用前景。
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