Human antimicrobial peptides in ocular surface defense

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Abstract

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.

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