Abstract:
Vitreomacular traction syndrome results from persistent vitreoretinal adhesions in the setting of partial posterior vitreous detachment (PVD). Vitrectomy and reattachment of retina is an effective therapeutic approach. The adhesion between vitreous cortex and internal limiting membrane (ILM) of the retina is stronger in youth, which brings difficulties to induce PVD in vitrectomy. Several clinical investigations demonstrated that intravitreous injection of plasmin before vitrectomy could reduce the risk of detachment. In our study, a novel recombinant human microplasminogen (rhμPlg) was expressed by Pichia pastoris. Molecular docking showed that the binding of rhμPlg with tissue plasminogen activator (t-PA) was similar to plasminogen, suggesting rh μPlg could be activated by t-PA to generate microplasmin (μPlm). Moreover, rhμPlg had higher catalytic activity than plasminogen in amidolytic assays. Complete PVD was found at vitreous posterior pole of 125 μg rhμPlg-treated eyes without morphological change of retina in juvenile rabbits via intraocular injection. Our results demonstrate that rhμPlg has a potential value in the treatment of vitreoretinopathy.
摘要:
玻璃体牵引综合征是在部分玻璃体后脱离(PVD)的情况下由持续性玻璃体视网膜粘连引起的。玻璃体切除术和视网膜复位是一种有效的治疗方法。玻璃体皮质与视网膜内界膜(ILM)之间的粘连在青年时期更强,这给玻璃体切除术中诱导PVD带来了困难。一些临床研究表明,玻璃体切除术前玻璃体内注射纤溶酶可以降低脱离的风险。在我们的研究中,巴斯德毕赤酵母表达了一种新的重组人微纤溶酶原(rhμPlg)。分子对接显示rhμPlg与组织纤溶酶原激活物(t-PA)的结合与纤溶酶原相似,提示rhμPlg可以被t-PA激活以产生微纤溶酶(μPlm)。此外,rhμPlg在酰胺分解试验中具有比纤溶酶原更高的催化活性。通过眼内注射,在125μgrhμPlg处理的眼睛的玻璃体后极处发现了完整的PVD,而幼年兔的视网膜形态没有变化。我们的结果表明,rhμPlg在玻璃体视网膜病变的治疗中具有潜在的价值。