Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Observational Study
. 2019 Dec 19;9(1):19447.
doi: 10.1038/s41598-019-55191-x.

Comprehensive expression patterns of inflammatory cytokines in aqueous humor of patients with neovascular age-related macular degeneration

Tomohito Sato  1 , Masaru Takeuchi  2 , Yoko Karasawa  1 , Kei Takayama  1 , Toshio Enoki  3
Affiliations
Observational Study

Comprehensive expression patterns of inflammatory cytokines in aqueous humor of patients with neovascular age-related macular degeneration

Tomohito Sato et al. Sci Rep. .

Abstract

Neovascular age-related macular degeneration (nAMD) is a complex and multi-factorial disease, and low-grade inflammation is associated with pathogenesis of nAMD. Aqueous humor could reflect intraocular immune environments in various eye diseases. The research so far used aqueous humor samples and revealed that inflammation is involved in pathophysiology of nAMD, although immunological roles of cytokines were evaluated inadequately with aspect to individual effects. Here we used 27 kinds of cytokines covering general immunologic reactions, examined specific expression patterns of cytokines, and assessed relationships between inflammation and pathophysiology of nAMD by multivariate analyses. In nAMD eyes, principal component analysis showed that IL-7, MCP-1, MIP-1β and VEGF had high principal component loadings of over 0.6 in the first principal component constituting 32.6% of all variability of the data. In exploratory factor analysis, IL-6, MCP-1 and MIP-1β had high factor loadings (FL) of over 0.5 in Factor 1 constituting 32.6% of all variability, while VEGF had FL of over 1.0 in Factor 3 constituting 10.7% of all variability. In hierarchical cluster analysis, MCP-1 and VEGF were located in the cluster of first proximate mutual distance to central retinal thickness. These data could suggest that low-grade inflammation is a principal contributor in nAMD.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Binomial logistic regression analysis of the contribution of aqueous humor cytokines to pathogenesis of nAMD. Risk factors of developing nAMD are shown in forest plot (A) and summary table (B) by binomial logistic regression analysis. CI; confidence interval, OR; odds ratio, *P < 0.05.
Figure 2
Figure 2
Expression patterns of aqueous humor cytokines by principal component analysis in nAMD patients and controls. Biplots of principal component loading (PCL) in first principle component (PC1) and second principle component (PC2) of nAMD patients (A) or controls (D) are presented. PCLs of the PC1 and PC2 in nAMD patients (B) or controls (E) are shown. Eigenvalues, contribution rates (CR) and cumulative contribution rates (CCR) of PC1 and PC2 in nAMD patients (C) or controls (F) are described. CCR; cumulative contribution ratio, CR; contribution ratio, PC; principle component, PCL; principal component loading, PC1; first principle component, PC2; second principle component.
Figure 3
Figure 3
Expression patterns of aqueous humor cytokines by exploratory factor analysis in nAMD patients. (A–C) Factor loadings (FL) of Factor1 (F1), Factor2 (F2) and Factor3 (F3) in nAMD eyes are drawn. (D–F) Biplots of FLs in F1, F2 and F3 are presented. (G) 3D-plots of FLs in F1, F2 and F3 are shown. (H) Eigenvalues, contribution rates and cumulative contribution rates of F1, F2 and F3 are described.
Figure 4
Figure 4
Expression patterns of aqueous humor cytokines by hierarchical cluster analysis in nAMD patients and controls. Heat maps of inflammatory cytokines in aqueous humor of nAMD patients (A) and controls (B) are presented. Color scale of cytokine levels denotes the following: low cytokine levels, red; middle to high cytokine levels, black to green.
See this image and copyright information in PMC

References

    1. Jager RD, Mieler WF, Miller JW. Age-related macular degeneration. N. Engl. J. Med. 2008;358:2606–2617. doi: 10.1056/NEJMra0801537. - DOI - PubMed
    1. Japanese Study Group of Polypoidal Choroidal Vasculopathy Criteria for diagnosis of polypoidal choroidal vasculopathy. Nippon Ganka Gakkai Zasshi. 2005;109:417–427. - PubMed
    1. Chen M, Xu H. Parainflammation, chronic inflammation, and age-related macular degeneration. J. Leukoc. Biol. 2015;98:713–725. doi: 10.1189/jlb.3RI0615-239R. - DOI - PMC - PubMed
    1. Liutkeviciene R, Lesauskaite V, Asmoniene V, Zaliuniene D, Jasinskas V. Factors determining age-related macular degeneration: a current view. Medicina (Kaunas) 2010;46:89–94. doi: 10.3390/medicina46020013. - DOI - PubMed
    1. Donoso LA, Kim D, Frost A, Callahan A, Hageman G. The role of inflammation in the pathogenesis of age-related macular degeneration. Surv. Ophthalmol. 2006;51:137–152. doi: 10.1016/j.survophthal.2005.12.001. - DOI - PMC - PubMed

Publication types

MeSH terms