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Chi-Chao Chan, DeFen Shen, Xiaoguang Cao, Vinson M. Wang, Yujuan Wang, Jingsheng Tuo; Expression Of IL-17 In Eyes Of Age-related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1228.
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While age-related macular degeneration (AMD) is not a classical inflammatory disease, inflammatory and immunological processes are shown to play an important role. Recently, Th17 type cytokines have been linked to neurodegenerative diseases such as multiple sclerosis and Alzheimer disease. Furthermore, the induction of serum Th17 cytokines is significantly elevated in both aged humans and mice. We studied IL-17 and IL-22 mRNA expression in the maculae of AMD patients and normal subjects, and in AMD choroidal neovascular membranes (CNVM). We compared ocular IL-17 levels between the C57BL/6 (WT) and Ccl2-/-/Cx3cr1-/- (DKO) mice, which develop AMD-like retinal lesions.
Macular cells (retina and choroid) from 5 geographic atrophic, 4 neovascular exudative AMD, and 4 age-matched normal archived eyes were microdissected and processed to measure IL-17 and IL-22 transcripts using quantitative RT-PCR. In addition, inflammatory cells were microdissected on the surgically excised CNVM from two AMD patients unresponsive to bevacizumab treatment. The eyes of DKO and WT at ages of 20 days, 2, 4, 7, and 12 months, were also isolated and measured for IL-17 mRNA levels by quantitative RT-PCR. The normalized difference in expression levels between universal human/mouse reference RNA and tested RNA was calculated as relative expression (ΔΔCT).
Significantly higher relative expression of IL-17 (AMD, 6.63±1.87 vs. control, 0.69±0.27, p < 0.006) and IL-22 (AMD, 28.82±7.31 vs. control, 5.56±1.93, p < 0.005) was measured in the AMD macular lesions compared to normal macula. However, there were no statistical differences between geographic and neovascular AMD. Moderately elevated IL-17 (7.89 and 0.50, respectively) and markedly elevated IL-22 expression (31.65 and 104.80, respectively) were found in the two CNVM. The age-related increase in IL-17 mRNA was observed in both DKO and WT mice. Moreover, significantly higher ocular IL-17 levels were also found in DKO compared to WT mice (p = 0.004, 0.036, 0.001, 0.033, 0.005, at 20 days, 2, 4, 7, and 12 months, respectively).
Aging and AMD-like degeneration are associated with increasing ocular IL-17 expression in mice. Significantly higher IL-17 and IL-22 expressions are detected in macular lesions with advanced AMD. Elevated Th17 type cytokines may contribute to the regulation of age-related inflammatory and neurodegenerative diseases including AMD.
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