Role of host-defence peptides in eye diseases

Abstract

The eye and its associated tissues including the lacrimal system and lids have evolved several defence mechanisms to prevent microbial invasion. Included among this armory are several host-defence peptides. These multifunctional molecules are being studied not only for their endogenous antimicrobial properties but also for their potential therapeutic effects. Here the current knowledge of host-defence peptide expression in the eye will be summarized. The role of these peptides in eye disease will be discussed with the primary focus being on infectious keratitis, inflammatory conditions including dry eye and wound healing. Finally the potential of using host-defence peptides and their mimetics/derivatives for the treatment and prevention of eye diseases is addressed.

Therapeutic Potential of the Antimicrobial Peptide OH-CATH30 for Antibiotic-Resistant Pseudomonas aeruginosa Keratitis

“…The therapeutic potential of AMPs has been actively studied in numerous bacterial infectious diseases, including skin infection, pneumonia, and peritonitis. However, few studies have focused on the topical application of naturally occurring AMPs to treat bacterial keratitis (12,17). In the current study, we investigated the potential application of a snake AMP (OH-CATH30) in ocular bacterial infection.…”

“…In another study, the synthetic peptide COL-1 demonstrated potent antimicrobial activity in vitro, but it was not effective in a rabbit model of P. aeruginosa keratitis and showed toxicity to rabbit corneas (19). Although the reason for the poor efficacy of the peptides in vivo is not well known, previous studies have demonstrated that the salt content of tears inhibits the antibacterial activity of some host defense peptides (12) the MPO in P. aeruginosa-infected mouse corneas, but it did not efficiently eradicate invading bacteria owing to its poor bactericidal activity against P. aeruginosa isolates in vitro (20). The protective efficacy of B-Lfcin in P. aeruginosa keratitis mainly depended on its anti-inflammatory properties and an increase in the antibacterial activity of CIP against multidrug-resistant P. aeruginosa.…”

“…Many AMPs have been found on the ocular surface, and they play critical roles in anti-infection and immunomodulation (12). Endogenous defensins 2 and 3 are required for host resistance against P. aeruginosa-induced corneal infection (13,14).…”

“…LL-37, the only human cathelicidin peptide, promotes high-glucoseattenuated epithelial wound healing via epidermal growth factor receptor transactivation in organ-cultured corneas (16). However, few studies have focused on the therapeutic potential of AMPs by topical application in bacterial keratitis, despite many investigations in other infectious diseases (12,17). The therapeutic efficacies of the synthetic peptides CA-M and COL-1 were investigated in a rabbit model of P. aeruginosa keratitis, and both peptides showed toxicity to the rabbit cornea and poor therapeutic efficacy (18,19).…”

Protective Role of Murine β-Defensins 3 and 4 and Cathelin-Related Antimicrobial Peptide in Fusarium solani Keratitis

“…Recent in vivo studies in a murine model of bacterial keratitis have shown that deficiency (either by transient silencing by short interfering RNA [siRNA] or gene knockout [KO]) of mouse ␤-defensin 2 (mBD2) or mBD3 (homolog of human ␤-defensin 2) or the cathelicidin cathelin-related antimicrobial peptide (CRAMP) (homolog of human LL37) results in more severe infection and tissue damage (23)(24)(25)(26). Further, exposure to Candida albicans significantly upregulated the expression of CRAMP (27), and mice deficient in CRAMP were more susceptible to Candida keratitis than wild-type (WT) mice (28).…”