Discrepant expression of cytokines in inflammation- and age-related cataract patients.

Wan Chen,Xiaojian Zhong,Zhaochuan Liu,Haotian Lin,Weirong Chen,Chufang Xie,Yu Geng,Matthaios Speletas

doi:10.1371/journal.pone.0109647

Abstract

PurposeInflammatory cataracts secondary to Behcet's disease (BD) or Vogt-Koyanagi-Harada disease (VKH) are thought to result from a pathological dysregulation of cytokines that is different from that of age-related (AR) cataracts. However, little is known about the function of cytokines in the development of inflammatory cataracts. The purpose of this study was to identify possible differences in cytokine expression in inflammation- and age-related cataract patients.MethodsAnalysis techniques involving the concomitant use of a cocktail of antibody-coated non-magnetic beads were used to determine the cytokine expression profiles of BD, VKH and AR cataract patients. Furthermore, anterior chamber aqueous flares and inflammatory cells were quantitatively measured with a laser flare cell meter (LFCM).ResultsThe expressions of interleukin-2 (IL-2), IL-4, IL-6, IL-10, IL-17A, and interferon-γ (IFN-γ) were analyzed in aqueous humor (AqH), phytohemagglutinin (PHA)-stimulated and non-PHA-stimulated cultures of peripheral blood mononuclear cells (PBMCs) from the three types of cataract patients. IL-6 and IFN-γ were identified above the detection limits, but, among the BD and VKH cataract patients, only the levels of IL-6 were significantly higher in both the AqH and PBMC non-PHA cultures compared with the levels observed in the AR cataract patients. In contrast, IFN-γ was significantly elevated in the AqH of the BD cataract patients compared with the VKH and AR cataract patients. In the PHA-stimulated PBMC cultures, IL-2, IFN-γ, IL-6, and IL-17A were significantly increased, and the IL-6 level was significantly higher in the VKH patients than in the BD and AR cataract patients. The correlation analyses of the cytokines and inflammation indexes of the AqH obtained with the LFCM revealed that only IL-6 was significantly correlated with the inflammation index.ConclusionDistinct expression profiles of cytokines and the correlations of these profiles with in vivo inflammatory indexes for inflammatory and AR cataract patients were identified.

Highlights

Cataracts secondary to uveitis, such as those that occur in Behcet’s disease (BD) and Vogt-Koyanagi-Harada disease (VKH), challenge ophthalmologists in many aspects, including a miotic pupil, iris atrophy, posterior synechiae, pupillary membrane, operation time, perioperative medication, macular edema, severe postoperative inflammation and band keratopathy
We inferred that there might be differences in the expression levels of IL-2, IL-4, IL-6, IL-10, IL-17A, and IFN-c between inflammatory cataracts that are secondary to BD and VKH and AR cataracts
The IL-2, IL-4, IL-10 and IL-17A contents were below the detection levels in the non-PHA-stimulated peripheral blood mononuclear cells (PBMCs) samples of the patients and the AR group

Summary

Introduction

Cataracts secondary to uveitis, such as those that occur in Behcet’s disease (BD) and Vogt-Koyanagi-Harada disease (VKH), challenge ophthalmologists in many aspects, including a miotic pupil, iris atrophy, posterior synechiae, pupillary membrane, operation time, perioperative medication, macular edema, severe postoperative inflammation and band keratopathy. The pathogenesis of this type of cataract is thought to be inflammationrelated, in contrast to the pathogenesis of age-related (AR) cataracts. [7] Previous studies have suggested that both BD and VKH are predominantly related to the Th1 immune response, and patients with these diseases have increased levels of Th1-associated cytokines, such as interferon-gamma (IFN-c), interleukin-12 (IL-12), and TNF-a. Previous studies have shown that aqueous flare can be detected in uveitis patients with long-standing inflammation even when that inflammation has been quiet for 3 months or longer. [15] there is likely to be differences in the aqueous flares and inflammatory cells of patients with BD and VKH cataracts relative to those with AR cataracts

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Conclusion