Larry A. Donoso Laboratory for Eye Research, Academic Section of Ophthalmology, Division of Clinical Neuroscience, School of Medicine, University of Nottingham, Queens Medical Centre, Derby Road, Nottingham NG7 2UH, United Kingdom.
Prog Retin Eye Res. 2017 Nov;61:1-22. doi: 10.1016/j.preteyeres.2017.03.004. Epub 2017 Jun 3.
Sight depends on the passage of light through the transparent cornea and being focused on the fovea. Its exposed position renders it vulnerable to microbial infection. The cornea has developed a wide array of defense mechanisms against infection, of which endogenous antimicrobial peptides (AMPs) are key. AMPs are essentially small molecular weight cationic peptides with a wide range of activity against virus, bacteria, fungi and parasites. Some proteins such as RNases and S100As are also included in this group. Several AMPs act synergistically allowing low expression of multiple AMPs to act efficiently. AMPs also have a range of non-microbicidal functions and serve as signaling molecules, immunomodulators; show anti-tumour activity, and influence vascularization and wound healing. Different toll-like receptors (TLR) have been implicated in the preferential induction of specific AMPs. A range of bacteria, including mycobacteria tuberculosis, viruses including herpes virus, fungi and parasites including acanthamoeba, that cause ocular infections have been shown to induce specific AMPs via TLR activation. Non-TLR mediated induction of AMP expression can occur and several molecules such as L-isoleucine, sodium butyrate, vitamin D3, phenylbutyrate, vasoactive intestinal peptide, and etinostat have been identified in this regard. Given the rising microbe resistance to antibiotics, the slow rate of development of new antibiotics and the limited access to effective antibiotics by patients living in the developing world, an ideal solution would be to find AMPs that are effective singly or in combination with each other or other antimicrobial proteins to reduce, if possible eliminate reliance on antibiotics alone.
视力取决于光线穿过透明的角膜并聚焦在黄斑上。它的暴露位置使其容易受到微生物感染。角膜已经开发出多种防御机制来抵御感染,其中内源性抗菌肽(AMPs)是关键。AMPs 本质上是具有广泛抗病毒、细菌、真菌和寄生虫活性的小分子阳离子肽。该组还包括一些蛋白质,如 RNases 和 S100As。一些 AMPs 协同作用,允许低表达的多种 AMPs有效地发挥作用。AMPs 还具有一系列非杀菌功能,作为信号分子、免疫调节剂;表现出抗肿瘤活性,并影响血管生成和伤口愈合。不同的 Toll 样受体(TLR)被认为与特定 AMP 的优先诱导有关。包括结核分枝杆菌在内的一系列细菌、包括单纯疱疹病毒在内的病毒、包括棘阿米巴在内的真菌和寄生虫,通过 TLR 激活已被证明可以诱导特定的 AMP。非 TLR 介导的 AMP 表达诱导也可能发生,并且已经在这方面鉴定了几种分子,如 L-异亮氨酸、丁酸钠、维生素 D3、苯丁酸钠、血管活性肠肽和埃替拉西。鉴于微生物对抗生素的耐药性不断上升、新抗生素的开发速度缓慢以及发展中国家的患者获得有效抗生素的机会有限,理想的解决方案是找到单独或联合使用的 AMPs,或者与其他抗菌蛋白一起使用,以减少(如果可能的话)对单独使用抗生素的依赖。