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Defense Proteins of the Ocular Surface

Ophthalmology, University of Louisville, Louisville, KY

Commercial Relationships: P.S. Steele, None; M.M. Jumblatt, None.

Grant Identification: EY13860–01

Abstract

Purpose:Recent evidence suggests that the ocular surface is an integral component of the mucosal immune system and that the diversity of ocular antimicrobial proteins is much greater than previously suspected. Mediators of innate mucosal host defense display functional similarities between the oral and ocular mucosae and have been investigated as to their overlapping distribution. Statherin, a proline–rich protein, participates in the defense of the oral cavity and contributes to the regulation of calcium homeostasis. CCL28, a mucosa–associated chemokine expressed in the salivary gland, contains sequence similarities to histatin at its C terminus and is both antimicrobial and chemotatic. We have shown by RT–PCR that histatins, small cationic histidine–rich peptides originally discovered in the salivary gland, are present in the lacrimal gland and secreted into the tear film. We therefore investigated the possibility that the protective effect of statherin and CCL28 extend to the ocular surface.

Methods:Human cornea and conjunctival tissues were collected from donors by the Kentucky Lions Eye Bank. Lacrimal glands were obtained from cadavers donated to the University of Louisville’s Fresh Tissue Laboratory. Total RNA was extracted and amplified by RT–PCR using primer pairs designed to amplify histatins, statherin, CCL28, and CCR10. cDNA products were identified by agarose gel electrophoresis, purified, cloned, and sequenced.

Results:Histatin, statherin, chemokine CCL28 and its ligand CCR10 transcripts are present in conjunctival and corneal tissues. Lacrimal glands, previously confirmed to express histatin cDNA, also express transcripts of these defense proteins.

Conclusions:ß defensins, histatins, and MUC7 have previously been identified as antimicrobial products of the ocular surface epithelium. We now show that the defense–type proteins statherin, CCL28 and CCR10 are produced by the cornea, conjunctiva, and lacrimal gland. Further studies are required to determine the cellular source of their synthesis and to demonstrate their presence in the normal tear film.

Keywords: cornea: tears/tear film/dry eye • conjunctiva • lacrimal gland

© 2004, The Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any part of this abstract, contact the ARVO Office at arvo{at}arvo.org.