Elsevier

Ophthalmology

Volume 111, Issue 12, December 2004, Pages 2186-2192
Ophthalmology

Original article
Conjunctival epithelial cell expression of interleukins and inflammatory markers in glaucoma patients treated over the long term

Presented at: American Academy of Ophthalmology annual meeting, November 17, 2003; Anaheim, California.
https://doi.org/10.1016/j.ophtha.2004.06.023Get rights and content

Purpose

To compare the conjunctival epithelial cell expressions of inflammatory cytokines in normal subjects and in glaucoma patients treated over the long term.

Design

Case–control study.

Participants

A total of 69 glaucoma patients treated over the long term and 15 normal subjects with no ocular abnormality or topical treatment.

Methods

Amongst the 69 glaucoma patients, 27 were treated with preserved β-blockers, 24 with unpreserved 0.5% timolol, and the other 18 patients with an association of ≥2 preserved drugs. All patients were treated for more than 1 year with the same treatment, with no significant differences between groups for mean ages and durations of treatment at the time of the study. Impression cytology specimens were taken and processed for immunofluorescence techniques. Conjunctival cell expressions of HLA DR, as a standard for inflammatory level, and the interleukins IL-6, IL-8, and IL-10 were obtained and quantified using flow cytometry.

Main outcome measures

Immune markers and proinflammatory cytokines in impression cytology specimens.

Results

We found a significantly increased expression of all immunoinflammatory markers and mediators in the conjunctival epithelium of glaucoma patients compared with normal eyes. Human leukocyte antigen DR was significantly higher in the 2 groups receiving preserved drugs than in the unpreserved timolol group. The 3 interleukins were similarly overexpressed in all glaucoma groups, with no significant between-groups differences except for the expression level of IL-8, which was significantly higher in the multitreatment group than in the preservative-free one.

Conclusions

The present study confirms the increased expression of immunoinflammatory markers by the conjunctival epithelium of glaucoma patients treated over the long term. The development of nontoxic preservatives or preservative-free solutions is therefore of great interest.

Section snippets

Patients

A total of 69 patients with glaucoma and 15 normal subjects were included in this case–control study conducted in compliance with the Declaration of Helsinki (Scotland amendment, 2000). All glaucoma patients had chronic primary open-angle glaucoma but no other ocular disease, as assessed after a complete ocular examination. They were treated for at least 1 year with the same treatment, 27 patients with preserved 0.5% timolol (containing 0.01% benzalkonium chloride as a preservative), 24

Results

The mean percentage of HLA DR–positive conjunctival cells (Fig 1A) was higher in both the preserved and the multitreatment groups (46.4% and 63.4%, respectively) than in the control group (13.1%; P<0.001 for both groups) and the eyes receiving preservative-free timolol (19.3%; P≤0.03 for both groups). No difference was found between the control and preservative-free groups. Although the mean percentage of HLA DR–positive cells was higher in the multitreatment group than in the preservative

Discussion

In previous studies on ocular surface immunopathology, some evidence has suggested that conjunctival epithelial cells may play an active role in ocular inflammation.28, 29, 30 Conjunctival epithelial cells have therefore previously been shown to express immune-related markers29, 32 and to be a possible source for proinflammatory cytokines.33, 34 Normal conjunctival epithelial cells express mRNA for IL-1, IL-6, IL-8, tumor necrosis factor α (TNF-α), and regulated-on-activation normal T-cell

References (49)

  • M. Pretolani et al.

    IL-10: a potential therapy for allergic inflammation?

    Immunol Today

    (1997)
  • P.J. Pisella et al.

    Prevalence of ocular symptoms and signs with preserved and preservative-free glaucoma medication

    Br J Ophthalmol

    (2002)
  • T. Ishibashi et al.

    Comparison of the short-term effects on the human corneal surface of topical timolol maleate with and without benzalkonium chloride

    J Glaucoma

    (2003)
  • D.C. Broadway et al.

    Adverse effects of topical antiglaucomatous medications on the conjunctiva

    Br J Ophthalmol

    (1993)
  • A.L. Dogan et al.

    Effects of topical antiglaucoma drugs on apoptosis rates of conjunctival epithelial cells in glaucoma patients

    Clin Experiment Ophthalmol

    (2004)
  • D.C. Broadway et al.

    Adverse effects of topical antiglaucomatous medicationII. The outcome of filtration surgery

    Arch Ophthalmol

    (1994)
  • I.S. Yalvac et al.

    Effects of antiglaucoma drugs on ocular surface

    Acta Ophthalmol Scand

    (1995)
  • H. Mietz et al.

    The effect of preservatives and antiglaucomatous medication on histopathology of the conjunctiva

    Graefes Arch Clin Exp Ophthalmol

    (1994)
  • B. Cvenkel et al.

    Ocular surface changes induced by topical antiglaucoma monotherapy

    Ophthalmologica

    (2002)
  • P.J. Pisella et al.

    Conjunctival proinflammatory and proapoptotic effects of latanoprost and preserved and unpreserved timolol: an ex vivo and in vitro study

    Invest Ophthalmol Vis Sci

    (2004)
  • M. De Saint Jean et al.

    Effects of benzalkonium chloride on growth and survival of Chang conjunctival cells

    Invest Ophthalmol Vis Sci

    (1999)
  • F. Becquet et al.

    Histopathological effects of topical ophthalmic preservatives on rat corneoconjunctival surface

    Curr Eye Res

    (1998)
  • C. Debbasch et al.

    Mitochondrial activity and glutathione injury in apoptosis induced by unpreserved and preserved beta-blockers on Chang conjunctival cells

    Invest Ophthalmol Vis Sci

    (2001)
  • M. Rolando et al.

    The effect of different benzalkonium chloride concentrations on human normal ocular surfaceA controlled prospective impression cytology study

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    Manuscript no. 240204.

    This study was supported by University Paris 6, Paris, France (grant no.: EA3123).

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