Abstract:
Pseudomonas aeruginosa is a leading cause of corneal infection both within India and globally, often causing a loss of vision. Increasing antimicrobial resistance among the bacteria is making its treatment more difficult. Preventing initial bacterial adherence to the host membrane has been explored here to reduce infection of the cornea. Synthetic peptides derived from human tetraspanin CD9 have been shown to reduce infection in corneal cells both in vitro, ex vivo and in vivo. We found constitutive expression of CD9 in immortalized human corneal epithelial cells by flow cytometry and immunocytochemistry. The synthetic peptides derived from CD9 significantly reduced bacterial adherence to cultured corneal epithelial cells and ex vivo human cadaveric corneas as determined by colony forming units. The peptides also significantly reduced bacterial burden in a murine model of Pseudomonas keratitis and lowered the cellular infiltration in the corneal stroma. Additionally, the peptides aided corneal wound healing in uninfected C57BL/6 mice compared to control mice. These potential therapeutics had no effect on cell viability or proliferation of corneal epithelial cells and have the potential to be developed as an alternative therapeutic intervention.
摘要:
铜绿假单胞菌是印度和全球角膜感染的主要原因,经常导致视力丧失。细菌中抗菌素耐药性的增加使其治疗更加困难。这里已经探索了防止初始细菌粘附到宿主膜以减少角膜感染。从人类四跨膜蛋白CD9衍生的合成肽已被证明可以在体外减少角膜细胞中的感染。离体和体内。我们通过流式细胞术和免疫细胞化学发现了CD9在永生化人角膜上皮细胞系中的组成型表达。如通过集落形成单位所确定的,衍生自CD9的合成肽显著降低细菌对培养的角膜上皮细胞和离体人尸体角膜的粘附。所述肽还显著降低了假单胞菌性角膜炎的鼠模型中的细菌负荷,并降低了角膜基质的细胞浸润。此外,与对照处理的小鼠相比,所述肽在未感染的C57BL/6小鼠中辅助角膜伤口愈合。这些潜在的疗法对细胞活力或角膜上皮细胞的增殖没有影响,并且有可能被开发为替代的治疗干预措施。