Abstract
Purpose: :
To investigate the expression of CCR4 and CCR5 chemokine receptors, as markers of the TH1 and TH2 pathways, and HLA DR class II antigen in impression cytology specimens of conjunctival cells obtained from patients with long–term glaucoma treatment in comparison to atopic and normal subjects.
Methods: :
In this case–controlled study, a total of 45 patients receiving long–term treatment for glaucoma, 20 suffering from vernal keratoconjunctivitis and 20 normal subjects with no ocular abnormality or topical treatment underwent impression cytology (IC) specimens. All patients gave their informed consent and study was performed under approval of Dijon and Paris–6 university Ethics Committees. Conjunctival cells were extracted and incubated with monoclonal antibodies to CCR4, CCR5, two chemokines related to the TH2 and TH1 systems, respectively, CD45 and HLA DR, in order to quantify conjunctival inflammation. They were processed for flow cytometry and analyzed in a masked manner.
Results: :
HLA DR was expressed at high levels in the glaucoma group, as previously described, but at very low levels in allergic and normal eyes. CD45 was expressed by only few cells in all three groups, with almost no significant differences. CCR4 was expressed at significantly higher levels in allergic and glaucomatous eyes than in the normal group. CCR5, in contrast, was significantly overexpressed in glaucomatous eyes, compared to the two other groups. Comparisons between groups, according to glaucoma drugs used, showed similar trends, with the lowest levels in patients receiving unpreserved drugs or prostaglandins, followed by preservative–containing beta–blockers and the highest inflammatory levels in multitreated eyes.
Conclusions: :
The immunoinflammatory reactions related to the TH1 or TH2 systems could be differentiated by the conjunctival CCR4/CCR5 profiles. Our results strongly evoke that, in contrast to allergic eyes involving as expected the TH2 pathway, long–term use of topical treatments may stimulate both TH1 and TH2 systems, suggesting a combination of allergic and inflammatory, most likely toxic, mechanisms. Interestingly, long term use of prostaglandins did not increase nor modified the overall inflammatory profile found in glaucoma patients.
Keywords: conjunctiva • drug toxicity/drug effects • flow cytometry