Host Defense Peptides at the Ocular Surface: Roles in Health and Major Diseases, and Therapeutic Potentials

Abstract

Sight is arguably the most important sense in human. Being constantly exposed to the environmental stress, irritants and pathogens, the ocular surface – a specialized functional and anatomical unit composed of tear film, conjunctival and corneal epithelium, lacrimal glands, meibomian glands, and nasolacrimal drainage apparatus – serves as a crucial front-line defense of the eye. Host defense peptides (HDPs), also known as antimicrobial peptides, are evolutionarily conserved molecular components of innate immunity that are found in all classes of life. Since the first discovery of lysozyme in 1922, a wide range of HDPs have been identified at the ocular surface. In addition to their antimicrobial activity, HDPs are increasingly recognized for their wide array of biological functions, including anti-biofilm, immunomodulation, wound healing, and anti-cancer properties. In this review, we provide an updated review on: (1) spectrum and expression of HDPs at the ocular surface; (2) participation of HDPs in ocular surface diseases/conditions such as infectious keratitis, conjunctivitis, dry eye disease, keratoconus, allergic eye disease, rosacea keratitis, and post-ocular surgery; (3) HDPs that are currently in the development pipeline for treatment of ocular diseases and infections; and (4) future potential of HDP-based clinical pharmacotherapy for ocular diseases.

Thymol Ameliorates Aspergillus fumigatus Keratitis by Downregulating the TLR4/ MyD88/ NF-kB/ IL-1β Signal Expression and Reducing Necroptosis and Pyroptosis

“…Fungus invasion causes innate and adaptive immune-mediated inflammation, leading to subsequent cornea tissue necrosis in the surrounding area [ 4 , 11 , 16 ]. Toll-like receptor 4 (TLR4) recognizes cell wall components of A. fumigatus [ 17 ], and recruits myeloid differentiation factor 88 (MyD88) molecules, which then causes nuclear factor-kappa B (NF-kB) to translocate to the nucleus and express pro-inflammatory and chemotactic cytokines [ 16 , 18 , 19 ]. These include CXCL8, CCL2, CCL3, and et al [ 20 , 21 ], which accumulates macrophages and neutrophils from limbus to infection site, and pro-IL-1β, which need to be actived [ 22 - 24 ].…”

Krein support vector machine classification of antimicrobial peptides

“…DBAASP contains peptide activity measurements against a wide-range of species, 58 including those of interest to us. We extracted from DBAASP all peptides with activity measured against S. aureus ATCC 29213, S. aureus ATCC 25923 or P. aeruginosa ATCC 27853 subject to the following conditions: (i) peptide length in the range [6,18], (ii) without intrachain bonds, (iii) without non-standard amino acids and (iv) MIC measured in mg mL −1 or mM. Condition (i) was imposed as that is the range of peptide lengths in our external test set.…”

“…AMPs, also known as host defense peptides, are a class of evolutionary conserved molecules that form an important component in the innate immune system. [4][5][6] These molecules are usually made of 12 to 50 amino acid residues, and they typically possess certain properties, including cationicity, 30-50% hydrophobicity, and amphiphilicity. They exhibit good antimicrobial activity against a broad range of bacteria, viruses, fungi, and parasites.…”

Advances of Antimicrobial Peptide‐Based Biomaterials for the Treatment of Bacterial Infections

“…Microbial keratitis is a common cause of ocular pain and visual impairment worldwide. [ 119 ] The cornea can be infected with a variety of pathogens, including S. aureus , P. aeruginosa , and Fusarium . [ 120 ] Topical antimicrobial therapy is the standard of care for ocular pathogenic infections compared to intra‐abdominal infections, which are complex, and skin infections, which have high proteolytic activity.…”

“…[ 128 ] The development of AMPs is ongoing and has shown encouraging results in the treatment of eye infections. [ 119b,129 ] Future research should focus on ways to reduce the development of drug resistance while adding a combination of in vitro and in vivo assessments.…”