MicroRNA-132调控青光眼滤过术后瘢痕化的研究

The most common reason for glaucoma filtration surgery failures is the excessive subconjunctival scarring, and angiogenesis plays an important role during the process. MicroRNA-132 (miR-132) has been identified as an angiogenic switch by targeting p120RasGAP in the endothelium and thereby inducing neovascularization. The aim of the current research is to investigate the effectiveness and safety of nanoparticle delivery anti-miR-132 in modulating wound healing after glaucoma filtration surgery. Human umbilical vein endothelial cells are transfected with anti-miR-132, and the expression of miR-132, cell proliferation, tube formation and cytotoxicity are measured and evaluated. The rabbit models of glaucoma filtration surgery with subconjunctival injections of anti-miR-132 are studied. Bleb survival and characteristics, intraocular pressure, and potential complications are evaluated. Histology of the surgical eye is performed to evaluate the expression of miR-132 and ocular scarring. This novel approach base on microRNAs may potentially be a new alternative for modulating wound healing after glaucoma filtration surgery, and provide new insight into other pathological angiogenesis related disorders.

青光眼滤过术后瘢痕化是导致手术失败的主要原因，新生血管在此过程中起重要作用。本课题基于血管生长调节因子microRNA-132(miR-132)，研究纳米载体介导下调miR-132对青光眼滤过术后瘢痕化的调控作用。以阳离子纳米聚合物CS-g-(PEI-b-mPEG)为载体构建和筛选miR-132抑制剂-纳米载体微粒，观察转染后对人脐静脉内皮细胞miR-132表达、细胞增殖、血管样结构形成的抑制效应及细胞毒性；建立兔青光眼滤过手术模型，对比球结膜下注射miR-132抑制剂对术后miR-132表达、滤过泡、眼压和滤过区血管和纤维化的影响，以及可能的毒副作用，揭示miR-132调控青光眼滤过术后瘢痕化的有效性和安全性。这是microRNAs在青光眼滤过术后瘢痕化研究领域的新应用，可望为青光眼滤过术后创伤愈合提供一种安全、有效的基因调控靶点，同时也为新生血管性疾病的防治提供新思路。

青光眼滤过术后瘢痕化是导致手术失败的主要原因。一系列复杂的动态生物学反应参与瘢痕形成过程，包括新生血管在此过程中起重要作用。MicroRNA-132 (miR-132)已被证明是靶向血管内皮细胞p120RasGAP的血管生成开关，进而诱导新生血管。本课题基于血管生长调节因子miR-132，研究下调miR-132 对青光眼滤过术后瘢痕化的调控作用。在体外，设计和合成miR-132 抑制剂，转染人脐静脉内皮细胞，结果表明随着miR-132抑制剂浓度的增加，人脐静脉内皮细胞miR-132的表达逐渐降低、对其增殖的抑制率增加。建立恒河猴滤过手术模型，与对照组相比，球结膜下注射miR-132 抑制剂可以明显延长滤过泡生存时间、维持更长的降眼压效应；同时球结膜下注射miR-132 抑制剂具有良好的耐受性。这是microRNAs 在青光眼滤过术后瘢痕化研究领域的新应用，可望为青光眼滤过术后创伤愈合提供一种安全、有效的基因调控靶点，同时也为新生血管性疾病的防治提供新思路。