Defensins and Other Antimicrobial Peptides at the Ocular Surface

Abstract

Although constantly exposed to the environment and "foreign bodies" such as contact lenses and unwashed fingertips, the ocular surface succumbs to infection relatively infrequently. This is, in large part, due to a very active and robust innate immune response mounted at the ocular surface. Studies over the past 20 years have revealed that small peptides with antimicrobial activity are a major component of the human innate immune response system. The ocular surface is no exception, with peptides of the defensin and cathelicidin families being detected in the tear film and secreted by corneal and conjunctival epithelial cells. There is also much evidence to suggest that the role of some antimicrobial peptides is not restricted to direct killing of pathogens, but, rather, that they function in various aspects of the immune response, including recruitment of immune cells, and through actions on dendritic cells provide a link to adaptive immunity. A role in wound healing is also supported. In this article, the properties, mechanisms of actions and functional roles of antimicrobial peptides are reviewed, with particular emphasis on the potential multifunctional roles of defensins and LL-37 (the only known human cathelicidin) at the ocular surface.

Diabetic retinopathy: Proteomic approaches to help the differential diagnosis and to understand the underlying molecular mechanisms

“…The chemical barrier contains mostly constitutively expressed AMPs, while some of them show inducible feature upon pathogenic or other stimuli. The tear fluid contains several prototypic AMPs such as defensins, dermcidin and LL-37 cathelicidin [74,85,101,102]. Defensins are small cationic peptides produced by epithelial cells with cysteine rich sequences forming a very stable 3D structure [103].…”

“…LL-37 cathelicidin is an α-helix type AMP of the tear fluid mainly produced by the corneal epithelial cells. Similar to the defensins, cathelicidin exerts various antimicrobial [102] and immunomodulatory functions [54] Complement C4b [64] Brain-specific angiogenesis inhibitor 1-associated protein 2 [70] Lysozyme C [38] VEGF [56] Complement C9 [64] Cystathionine b-synthase [70] Lipophilin A [38] Complement factor B [64] MMP-13 [70] Immunoglobulin lambda chain [38] Pigment epithelial-derived factor [64] Podocan [70] Hsp27 [76] Interstitial retinol-binding protein [64] Selenoprotein P [70] β 2 -Microglobulin [76] Inter-α trypsin inhibitor heavy chain [64] Enolase [77] [95]. In addition, it has an important role in re-epithelialization during wound healing [107].…”

Human Defensins: Potential Tools for Clinical Applications

“…To date, four hBDs were isolated (hBD-1-4) [2,34]. These antimicrobial peptides display their bactericidal activity against Gram-positive and -negative bacteria [11,12,[35][36][37].…”

“…Alpha-defensins enhance the migration of T-cells [62,63], while human β-defensins have chemotactic effects on dendritic cells [17,62]. HNP1-3 and hBD-1 exhibit chemotactic functions for monocytes [34]. HBD-2 is a chemotactic peptide for human neutrophils stimulated with TNF-α [60] as well as macrophages [34] and it also acts as a chemotaxin for human mast cells [34,59].…”

“…HNP1-3 and hBD-1 exhibit chemotactic functions for monocytes [34]. HBD-2 is a chemotactic peptide for human neutrophils stimulated with TNF-α [60] as well as macrophages [34] and it also acts as a chemotaxin for human mast cells [34,59]. In addition, hBDs function as important chemotactic agents for immature dendritic cells [64].…”