TGF-β2诱导高度近视眼小梁网重塑导致白内障术后早期眼压升高的机制研究
批准号:
82101100
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:
齐姣
依托单位:
学科分类:
晶状体与白内障
结题年份:
2024
批准年份:
2021
项目状态:
已结题
项目参与者:
齐姣
中文摘要
高度近视白内障是一种高致盲风险的复杂白内障,容易出现白内障术后早期眼压升高的并发症,但具体机制仍然未知。我们前期研究发现,小梁网狭窄是高度近视白内障术后早期眼压升高的解剖学因素,诱导小梁网重塑的关键因子TGF-β2在高度近视眼中高表达并与术后早期眼压升高密切相关。于是我们推测:高度近视眼前节组织高表达的TGF-β2诱导小梁网重塑,从而导致房水流出通道狭窄,使其在白内障术后早期出现眼压升高。因此本项目拟首先在人群层面明确高度近视眼房水中TGF-β2浓度、小梁网结构和白内障术后早期眼压升高三者的相关性。然后进一步从细胞层面培养TGF-β2处理的小梁网细胞、动物层面构建小鼠离焦高度近视模型并行晶状体囊外摘除术,以研究高度近视眼中TGF-β2调节小梁网细胞凋亡、上皮间叶转化、细胞外基质分泌的具体过程,及其对术后眼压的影响。旨在阐明高度近视眼白内障术后早期眼压升高的具体机制,为其防治奠定重要基础。
英文摘要
Highly myopic cataract is a type of complicated cataract with high risk of blindness. The early intraocular pressure spike after cataract surgery is common in highly myopic cataract eyes, which mechanism is still unknown. Based on our previous studies, we found that the trabecular meshwork stenosis is its anatomical factor. TGF-β2 (transforming growth factor-beta2), a key factor inducing trabecular meshwork remodeling, is highly expressed in highly myopic eyes and is closely related to the postoperative intraocular pressure spike. Therefore, we speculated that the highly expressed TGF-β2 in the anterior segment tissue of highly myopic eyes induces the trabecular meshwork remodeling, which leads to the narrowing of the aqueous humor outflow facility, resulted in the postoperative intraocular pressure spike. Thus, this project intends to clarify the correlations among the concentration of TGF-β2 in aqueous fluid, structure of trabecular meshwork and postoperative intraocular pressure spike in highly myopic cataract patients firstly. Then, we further cultivate the TGF-β2 treated trabecular meshwork cells, and establish the animal model of experimental high myopia with performed extracapsular lens extraction to investigate the process of TGF-β2 regulating trabecular meshwork cell apoptosis, epithelial-mesenchymal transition, and extracellular matrix secretion in highly myopic eyes, and its impact on postoperative intraocular pressure. We aim to clarify the mechanism of the early intraocular pressure spike after cataract surgery in highly myopic cataract eyes, which lays an important groundwork for its prevention and treatment.
高度近视白内障是一种具有高致盲风险的复杂白内障,成为了现在危害人群视力健康的主要疾病。我们前期研究发现,术后早期眼压升高是高度近视白内障患者白内障术后常见的并发症,小梁网狭窄是高度近视白内障术后早期眼压升高的解剖学因素。但是,具体发生机制仍然未知。因此,本项目研究目的聚焦于高度近视白内障术后眼压升高的发生机制。本项目首先在人群层面检测房水细胞因子,并与术后眼压升高进行相关性分析,明确了TGF-β2和MCP-1是高度近视白内障术后眼压升高相关的房水细胞因子;然后,以近视造模小鼠研究高度近视眼小梁网重塑机制,并用TGF-β2高表达的小梁网细胞模拟高度近视眼小梁网细胞,激素处理模拟白内障术后激素用药状态,明确了高度近视眼高表达的TGF-β2对小梁网重塑的具体作用机制;最后,利用MCP-1基因敲除的近视造模小鼠,明确了高度近视眼内高浓度MCP-1导致其血房水屏障破坏的具体作用机制。综合本项目研究结果,阐明了高度近视眼中一方面高浓度的TGF-β2导致小梁网重塑使得房水流出通道狭窄,另一方面高浓度的MCP-1破坏血房水屏障导致房水流出需求增大,最终导致高度近视眼白内障术后容易出现眼压升高。本课题的科学意义在于为高度近视白内障术后眼压升高的预测和治疗奠定基础和提供实验数据支持。
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