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. 2015 Mar 26;10(3):e0122184.
doi: 10.1371/journal.pone.0122184. eCollection 2015.

T-helper1/T-helper2 cytokine imbalance in the iris of patients with glaucoma

ManSin Wong  1 , Ping Huang  1 , Weiyi Li  2 , Ying Li  1 , Samuel S Zhang  3 , Chun Zhang  1
Affiliations

T-helper1/T-helper2 cytokine imbalance in the iris of patients with glaucoma

ManSin Wong et al. PLoS One. .

Abstract

The mechanistic study of glaucoma pathogenesis has shifted to seeking to understand the effects of immune responses on retinal ganglion cell damage and protection. Cytokines mediate the biological effects of the immune system, and our previous study revealed an imbalance of T-helper (Th) 1-derived and Th2-derived cytokines in the serum of patients with glaucoma. In this study, we collected irises from normal individuals and patients with primary open-angle closure (POAG) or chronic angle-closure glaucoma (CACG). We used real-time polymerase chain reaction (PCR) to measure the expression of Th1 (interleukin (IL)-2, interferon-gamma (IFN-γ)), Th2 (IL-4, IL-6, IL-10), and Th3 (transforming growth factor-beta (TGF-β)) cytokines. We then performed immunohistochemical staining to characterize the localization of the upregulated cytokines in iris cryosections. We observed an upward trend in the expression of IL-2 and IFN-γ and a downward trend in IL-6 expression in the iris of POAG and CACG patients. Expression of TGF-β also increased. Immunohistochemistry revealed that IL-2 expression in POAG and CACG patients was localized in the anterior surface of the blood vessel wall in the stroma of the iris, in the cytoplasm of some cells, in the anterior epithelium, and in the posterior pigment epithelium. These findings indicate that immune status differed between the iris tissues of POAG and CACG patients and those of normal individuals. A T-helper cytokine imbalance may modulate the immune microenvironment in glaucomatous eyes and thus influence optic neuropathy.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Interleukin (IL)-2, IL-6, interferon-gamma (IFN-γ), and transforming growth factor-beta (TGF-β) in the irises of primary open-angle glaucoma (POAG) and chronic angle-closure glaucoma (CACG) patients and control subjects.
Differences between groups were analyzed by ANOVA Least Significant Difference test. P value ≤ 0.05 was considered statistically significant. Mean concentrations of IL-2, IFN-γ, and TGF-β showed an upward trend in the iris of POAG and CACG patients. A downward trend of IL-6 was observed in the irises of POAG and CACG patients.
Fig 2
Fig 2. Interferon-gamma (IFN-γ) status in sections of human iris, as shown by AEC staining.
Results for IFN-γ were negative in all examined iris sections. Scale bar, 50 μm
Fig 3
Fig 3. Transforming growth factor-beta (TGF-β) status in sections of human iris, as shown by AEC staining.
TGF-β results were negative in all examined iris sections. Scale bar, 50 μm
Fig 4
Fig 4. Interleukin (IL)-2 status in sections of human iris, as shown by AEC staining.
IL-2 results were negative in the control subjects and positive in the primary open-angle glaucoma (POAG) and chronic angle-closure glaucoma (CACG) patients. Positive staining was localized to the anterior surface of the iris, the blood vessel wall in the stroma, the cytoplasm of some cells, and the posterior pigment epithelium. Scale bar, 50 μm
See this image and copyright information in PMC

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