Novel Peptides with Dual Properties for Treating Pseudomonas aeruginosa Keratitis: Antibacterial and Corneal Wound Healing.

Novel Peptides with Dual Properties for Treating Pseudomonas aeruginosa Keratitis: Antibacterial and Corneal Wound Healing.
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DOI:
10.3390/biom13071028
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发表时间:
2023-06-23
期刊:
影响因子:
5.5
通讯作者:
--
中科院分区:
生物学2区
文献类型:
--
作者:

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角膜上皮是眼睛前部的一层,其有助于将光折射到视网膜上并有助于眼部免疫防御。虽然完整的角膜上皮是抵抗微生物病原体和损伤的极好屏障,但角膜擦伤可导致毁灭性的眼部感染。其中,铜绿假单胞菌相关性角膜炎常导致角膜组织严重恶化,甚至失明。因此,非常需要发现不仅能够根除通常对抗生素具有抗性的眼部感染,而且能够引起角膜伤口修复的新药。最近,我们证明了两个肽,ESC(1-21)和它的非对映体ESC(1-21)-1c的有效的抗假单胞菌活性。在这项研究中,通过铜绿假单胞菌角膜炎的小鼠模型和体内角膜清创伤口,我们发现了这些肽,特别是ESC(1-21)-1c,治愈角膜炎和促进角膜伤口愈合的功效。后一种性质也得到了体外细胞划痕和ELISA测定的支持。总的来说,目前的研究强调了ESC肽作为治疗角膜感染和损伤的新型眼科药物,能够显示出抗菌和伤口愈合的双重功能,在相同的微摩尔浓度范围内很少在单一肽中发现。
The corneal epithelium is a layer in the anterior part of eye that contributes to light refraction onto the retina and to the ocular immune defense. Although an intact corneal epithelium is an excellent barrier against microbial pathogens and injuries, corneal abrasions can lead to devastating eye infections. Among them, Pseudomonas aeruginosa-associated keratitis often results in severe deterioration of the corneal tissue and even blindness. Hence, the discovery of new drugs able not only to eradicate ocular infections, which are often resistant to antibiotics, but also to elicit corneal wound repair is highly demanded. Recently, we demonstrated the potent antipseudomonal activity of two peptides, Esc(1-21) and its diastereomer Esc(1-21)-1c. In this study, by means of a mouse model of P. aeruginosa keratitis and an in vivo corneal debridement wound, we discovered the efficacy of these peptides, particularly Esc(1-21)-1c, to cure keratitis and to promote corneal wound healing. This latter property was also supported by in vitro cell scratch and ELISA assays. Overall, the current study highlights Esc peptides as novel ophthalmic agents for treating corneal infection and injury, being able to display a dual function, antimicrobial and wound healing, rarely identified in a single peptide at the same micromolar concentration range.
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