Abstract:
Choroidal neovascularization (CNV) is a common ocular pathology that may be associated in a variety of eye diseases. Although intravitreal injection treatment of anti-vascular endothelial growth factor (anti-VEGF) drugs shows significant clinical benefits in CNV treatment, the limitations of the current therapy need to be addressed. The aim of our study was to investigate the potential utility of three C-end Rule (CendR) peptides (RPARPAR, PL3, iRGD) for CNV targeting and to evaluate the efficacy of peptides for treating experimental CNV in mice. We observed that the CendR peptides localize to the CNV lesion sites after intravitreal injection and were mainly found in the outer nuclear cell layer (ONL) of the mouse retina. Interestingly, experimental therapy with tenascin-C (TNC-C) and neuropilin-1 (NRP-1)-targeting PL3 peptide, reduced angiogenesis and decreased vascular leakage. The results suggest that PL3 and potentially other CendR peptides could serve as affinity targeting ligands and therapeutics for ocular diseases that involve pathological CNV.
摘要:
脉络膜新生血管(CNV)是一种常见的眼部病理,可能与多种眼部疾病有关。尽管玻璃体内注射抗血管内皮生长因子(抗VEGF)药物在CNV治疗中显示出显著的临床益处,目前治疗的局限性需要解决.我们研究的目的是研究三种C端规则(CendR)肽(RPARPAR,PL3,iRGD)用于CNV靶向,并评估肽治疗小鼠实验性CNV的功效。我们观察到CendR肽在玻璃体内注射后定位于CNV病变部位,并且主要在小鼠视网膜的外核细胞层(ONL)中发现。有趣的是,生腱蛋白-C(TNC-C)和神经纤毛蛋白-1(NRP-1)靶向PL3肽的实验治疗,减少血管生成和减少血管渗漏。结果表明,PL3和潜在的其他CendR肽可以用作涉及病理性CNV的眼部疾病的亲和靶向配体和治疗剂。