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Antimicrobial peptides in human corneal tissue of patients with fungal keratitis
  1. Imran Mohammed1,
  2. Debasmita Mohanty2,
  3. Dalia G. Said1,3,
  4. Manas Ranjan Barik4,
  5. Mamatha M Reddy4,
  6. Ahmed Alsaadi5,
  7. Sujata Das6,
  8. Harminder Singh Dua1,3,
  9. Ruchi Mittal2
  1. 1Academic Ophthalmology, Division of Clinical Neuroscience, School of Medicine, University of Nottingham, Nottingham United Kingdom
  2. 2Kanupriya Dalmia Ophthalmic Pathology Laboratory, L V Prasad Eye Institute, MTC Campus, Bhubaneswar, India
  3. 3Ophthalmology Department, Nottingham University Hospitals, Queens Medical Centre, Nottingham United Kingdom
  4. 4Ocular Microbiology Service, L V Prasad Eye Institute, MTC Campus, Bhubaneswar, India
  5. 5Ophthalmology Department, Zayed Military Hospital, Abu Dhabi, United Arab Emirates
  6. 6Cornea and Anterior Segment Service, L V Prasad Eye Institute, MTC Campus, Bhubaneswar, India
  1. Correspondence to Harminder Singh Dua, Ophthalmology, University of Nottingham, Queens Medical Centre, B Floor, Eye & ENT Building, Derby Road, Nottingham NG7 2UH, UK; Harminder.Dua{at}nottingham.ac.uk; profdua{at}gmail.com

Abstract

Background Fungal keratitis (FK) is the leading cause of unilateral blindness in the developing world. Antimicrobial peptides (AMPs) have been shown to play an important role on human ocular surface (OS) during bacterial, viral and protozoan infections. In this study, our aim was to profile a spectrum of AMPs in corneal tissue from patients with FK during the active pase of infection and after healing.

Methods OS samples were collected from patients at presentation by impression cytology and scraping. Corneal button specimens were collected from patients undergoing therapeutic penetrating keratoplasty for management of severe FK or healed keratitis. Gene expression of human beta-defensin (HBD)-1, -2, -3 and -9, S100A7, and LL-37 was determined by quantitative real-time PCR.

Results Messenger RNA expression (mRNA) for all AMPs was shown to be significantly upregulated in FK samples. The levels of HBD-1 and -2 mRNA were found to be elevated in 18/20 FK samples. Whereas mRNA for HBD-3 and S100A7 was upregulated in 11/20 and HBD9 was increased in 15/20 FK samples. LL-37 mRNA showed moderate upregulation in 7/20 FK samples compared with controls. In healed scar samples, mRNA of all AMPs was found to be low and matching the levels in controls.

Conclusion AMP expression is a consistent feature of FK, but not all AMPs are equally expressed. HBD-1 and -2 are most consistently expressed and LL-37 the least, suggesting some specificity of AMP expression related to FK. These results will help to identify HBD sequence templates for designing FK-specific peptides to test for therapeutic potential.

  • Cornea
  • Experimental & laboratory
  • Infection
  • Immunology
  • Microbiology
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Footnotes

  • HD and RM contributed equally

  • IM and DM contributed equally

  • Funding This work was finacially supported by the Fight for Sight small grant award (Ref: 5007/08) to HSD and IM.

  • Competing interests HSD: Honoraria and Travel expenses from Allergan, Arctic Vision, Croma, Dompe, Santen, Thea. Shares in NuVision Biotherapies and GlaxoSmithKline.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement There are no additional unpublished data.

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