A novel antimicrobial peptidoglycan recognition protein in the cornea

Invest Ophthalmol Vis Sci. 2009 Sep;50(9):4185-91. doi: 10.1167/iovs.08-3040. Epub 2009 Apr 22.

Abstract

Purpose: In an earlier gene expression study, the authors identified a novel antimicrobial gene, Peptidoglycan recognition protein 1 (Pglyrp1), in the mouse cornea. Here the expression of the Pglyrp1 transcript and the encoded protein, PGLYRP1, in the cornea was investigated. The role of PGLYRP1 in the cornea was further investigated using wild-type and Pglyrp1-deficient mice. This is the first report of this antimicrobial protein in the cornea.

Methods: PGLYRP1 was detected in the cornea and was further localized to the epithelium by immunohistology, confocal microscopy, immunoblotting, and real-time PCR. The role of PGLYRP1 in the cornea was investigated by comparing the response of wild-type and Pglyrp1(-/-) mice to corneal epithelial wounds and Pseudomonas aeruginosa-mediated corneal infections. The antibacterial effects of corneal PGLYRP1 were assayed by measuring bacterial growth in vitro, in the presence of wild-type corneal epithelial extracts, before and after antibody-mediated blocking of PGLYRP1.

Results: PGLYRP1 is expressed at high levels in the mouse corneal epithelium. PGLYRP1 was localized to the mouse corneal epithelium and the human corneal epithelium. The Pglyrp1(-/-) mouse shows delayed healing and poor clearing of bacterial keratitis; in vitro its epithelial protein extract shows reduced bacteriostatic activity compared with wild-type mice.

Conclusions: PGLYRP1 is a novel antimicrobial protein of the corneal epithelium and protects the ocular surface from bacterial infections.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Anti-Infective Agents / metabolism*
  • Anti-Infective Agents / pharmacology
  • Colony Count, Microbial
  • Corneal Ulcer / microbiology
  • Corneal Ulcer / prevention & control*
  • Cytokines / pharmacology
  • Cytokines / physiology*
  • Epithelium, Corneal / metabolism*
  • Escherichia coli / drug effects
  • Eye Infections, Bacterial / microbiology
  • Eye Infections, Bacterial / prevention & control*
  • Humans
  • Immunoblotting
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Microscopy, Confocal
  • Pseudomonas Infections / microbiology
  • Pseudomonas Infections / prevention & control*
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Wound Healing / drug effects

Substances

  • Anti-Infective Agents
  • Cytokines
  • Pglyrp1 protein, mouse
  • RNA, Messenger