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Increased Expression of Hepcidin and Toll-Like Receptors 8 and 10 in Viral Keratitis

Mohammed, Imran BPharm, MSc, PhD*; Abedin, Asiya FRCS Ophth (Ed)*; Tsintzas, Kostas PhD†; Abedin, Syed A MRCS (Eng)‡; Otri, Ahmad M MD*; Hopkinson, Andrew PhD*; Mathew, Manu MRCOphth*; Dua, Harminder S MD, PhD*

doi: 10.1097/ICO.0b013e31820126e5
Basic Investigation

Purpose: Antimicrobial peptides (AMPs) and toll-like receptors (TLRs) form part of the “chemical barrier” of the ocular surface to microbes. Evidence suggests that pathogen recognition by TLR releases AMPs, altering AMP-TLR profiles in pathological states. This study investigated ocular surface expression of AMP-TLRs in health and disease.

Methods: Complementary DNA from conjunctival and corneal impression cytology samples was used for semiquantitative and quantitative polymerase chain reactions, to determine gene expression of 6 AMPs and TLRs-1-10, in healthy subjects and patients with bacterial (n = 6), viral (n = 6), Acanthamoeba (n = 3), or dry eye (n = 7) diseases.

Results: Semiquantitative polymerase chain reaction showed variable AMP expression within groups and some expression patterns between groups, increased levels of LEAP (liver-expressed antimicrobial peptide)-1/hepcidin in viral disease, LEAP-2 in dry eye, and human beta defensin 3 in bacterial disease. There was no significant variability in TLR expression. Quantitative polymerase chain reaction showed significantly higher expression of LEAP-1 (P = 0.002) and TLR-8 (P = 0.023) and TLR-10 (P = 0.014) in viral keratitis and LEAP-2 (P = 0.034) in dry eye, versus controls.

Conclusions: Increased expression of LEAP-1 and TLRs 8 and 10 in viral keratitis is novel; TLR-10 has not previously had a documented ligand. LEAP-2 may have a role in dry eye. Further studies will help to improve the understanding of these diseases and yield novel therapeutic interventions.

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From the *Larry A Donoso Laboratory for Eye Research, Academic Division of Ophthalmology, ENT Centre and †School of Biomedical Sciences, University of Nottingham, Nottingham, United Kingdom; and ‡Department of Endocrinology and Metabolism, Institute of Biomedical Research, University of Birmingham, Birmingham, United Kingdom.

Supported by a grant from the Royal Blind Asylum and School/Scottish National Institution for the War Blinded and Royal College of Surgeons of Edinburgh, United Kingdom and the British Eye Research Foundation and Fight for Sight PhD studentship to I. Mohammed.

I. Mohammed and A. Abedin should be considered joint first authors.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.corneajrnl.com).

Reprints: Prof Harminder S. Dua, Division of Ophthalmology and Visual Sciences, Eye and ENT Centre, Queens Medical Centre campus, University Hospital, Nottingham NG7 2UH United Kingdom (e-mail: harminder.dua@nottingham.ac.uk).

© 2011 Lippincott Williams & Wilkins, Inc.