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Detection of Chemokine Receptor CCR5 on Conjunctival Epithelial Cells in Keratocojunctivitis Sicca

¹ Ophthalmology, Schepens Eye Research Institute. Harvard, Boston, MA, United States

Commercial Relationships: A. Sood, None; P. Argueso, None; S. Michaud, None; A. Tisdale, None; I.K. Gipson, None; R. Dana, Allergan,Inc. C, R.

Abstract

Purpose: Immune-based inflammation as evidenced by upregulation of HLA-DR, CD40 and its ligand (CD40L), and adhesion molecules (ICAM-1) on resident ocular surface epithelial cells has been demonstrated in keratoconjunctivitis sicca (KCS) or dry eye syndrome. Chemokines are chemotactic cytokines, which, along with adhesion molecules, regulate immunoinflammatory responses in tissues. The purpose of the current study is to analyze the cell surface expression of select (CC or beta) chemokine receptors on conjunctival epithelial cells in normal and dry eye patients.
Method: Conjunctival impression cytology specimens were collected from normal human subjects (N=10) and dry eye patients (N=20) after a detailed clinical evaluation. The presence of chemokine receptor CCR5 was studied by flow cytometry on cells from impression cytology samples using immunocytological staining techniques. Immunofluorescence of chemokine receptor CCR5 was also studied on cells on cytospin slides obtained from impression cytology specimen and conjuctival biopsies from normal human subjects.
Results: Immunofluorescence studies showed positive binding of CCR5 antibody to conjunctival epithelial cells in normal conjunctival biopsies and cytospin slides. By flow cytometry, we found an increased conjunctival cell surface expression of chemokine receptor CCR5 in samples from dry eye patients compared to normals. We also found by flow cytometry that this increased expression of CCR5 in dry eye patients was more so on the resident epithelial cells compared to infiltrating bone marrow derived CD45+ cells.
Conclusion: Our finding of increased presence of CCR5 on resident epithelial cells from dry eye patients suggests the potential role for these cells in recruiting T cells or in modulating the immune response given the critical role of CCR5 in mediating T-helper-1 type responses. These data provide a rationale for chemokine receptor blockade as a therapeutic modality in dry eye syndrome.

Keywords: conjunctiva • cornea: tears/tear film/dry eye • inflammation

© 2003, 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.