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      Dry Eye as a Mucosal Autoimmune Disease

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          Abstract

          Dry eye is a common ocular surface inflammatory disease that significantly affects quality of life. Dysfunction of the lacrimal function unit (LFU) alters tear composition and breaks ocular surface homeostasis, facilitating chronic inflammation and tissue damage. Accordingly, the most effective treatments to date are geared towards reducing inflammation and restoring normal tear film. The pathogenic role of CD4+ T cells is well known, and the field is rapidly realizing the complexity of other innate and adaptive immune factors involved in the development and progression of disease. The data support the hypothesis that dry eye is a localized autoimmune disease originating from an imbalance in the protective immunoregulatory and proinflammatory pathways of the ocular surface.

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          Preferential recruitment of CCR6-expressing Th17 cells to inflamed joints via CCL20 in rheumatoid arthritis and its animal model

          Keiji Hirota, Hiroyuki Yoshitomi, Motomu Hashimoto … (2007)
          This report shows that interleukin (IL) 17–producing T helper type 17 (Th17) cells predominantly express CC chemokine receptor (CCR) 6 in an animal model of rheumatoid arthritis (RA). Th17 cells induced in vivo in normal mice via homeostatic proliferation similarly express CCR6, whereas those inducible in vitro by transforming growth factor β and IL-6 additionally need IL-1 and neutralization of interferon (IFN) γ and IL-4 for CCR6 expression. Forced expression of RORγt, a key transcription factor for Th17 cell differentiation, induces not only IL-17 but also CCR6 in naive T cells. Furthermore, Th17 cells produce CCL20, the known ligand for CCR6. Synoviocytes from arthritic joints of mice and humans also produce a large amount of CCL20, with a significant correlation (P = 0.014) between the amounts of IL-17 and CCL20 in RA joints. The CCL20 production by synoviocytes is augmented in vitro by IL-1β, IL-17, or tumor necrosis factor α, and is suppressed by IFN-γ or IL-4. Administration of blocking anti-CCR6 monoclonal antibody substantially inhibits mouse arthritis. Thus, the joint cytokine milieu formed by T cells and synovial cells controls the production of CCL20 and, consequently, the recruitment of CCR6+ arthritogenic Th17 cells to the inflamed joints. These results indicate that CCR6 expression contributes to Th17 cell function in autoimmune disease, especially in autoimmune arthritis such as RA.
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            Prevalence of dry eye syndrome among US women.

            Debra Schaumberg, David A. Sullivan, Julie Buring … (2003)
            Dry eye syndrome (DES) is believed to be one of the most common ocular problems in the United States (US), particularly among older women. However, there are few studies describing the magnitude of the problem in women and how this may vary with demographic characteristics. Cross-sectional prevalence survey. we surveyed 39,876 US women participating in the Women's Health Study about a history of diagnosed DES and dry eye symptoms. we defined DES as the presence of clinically diagnosed DES or severe symptoms (both dryness and irritation constantly or often). We calculated the age-specific prevalence of DES and adjusted the overall prevalence to the age distribution of women in the US population. We used logistic regression to examine associations between DES and other demographic factors. The prevalence of DES increased with age, from 5.7% among women or = 75 years old. The age-adjusted prevalence of DES was 7.8%, or 3.23 million women aged > or = 50 in the US. Compared with Whites, Hispanic (odds ratio [OR] = 1.81, confidence interval [CI] = 1.18-2.80) and Asian (OR = 1.77, CI = 1.17-2.69) women were more likely to report severe symptoms, but not clinically diagnosed DES. There were no significant differences by income (P([trend]) =.78), but more educated women were less likely to have DES (P([trend]) =.03). Women from the South had the highest prevalence of DES, though the magnitude of geographic differences was modest. Dry eye syndrome leading to a clinical diagnosis or severe symptoms is prevalent, affecting over 3.2 million American women middle-aged and older. Although the condition is more prevalent among older women, it also affects many women in their 40s and 50s. Further research is needed to better understand DES and its impact on public health and quality of life.
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              Prevalence of dry eye disease among US men: estimates from the Physicians' Health Studies.

              Debra Schaumberg, Thomas D. Sullivan, Reza Dana … (2009)
              To estimate the prevalence and risk factors for dry eye disease (DED) among US men. Cross-sectional prevalence survey among male participants 50 years and older in the Physicians' Health Studies I (N = 18,596) and II (N = 6848). We defined DED as the presence of clinically diagnosed dry eye or severe symptoms (both dryness and irritation constantly or often). We calculated the age-standardized prevalence of DED adjusted to the age distribution of US men in 2004 and projected estimates forward to 2030. We compared DED prevalence with a similar cohort of women and examined associations with possible risk factors. The prevalence of DED increased with age, from 3.90% among men aged 50 to 54 years to 7.67% among men 80 years and older (P for trend <.001). High blood pressure (odds ratio, 1.28; 95% confidence interval, 1.12-1.45) and benign prostatic hyperplasia (odds ratio, 1.26; 95% confidence interval, 1.09-1.44) were associated with a higher risk of DED. Use of antidepressants, antihypertensives, and medications to treat benign prostatic hyperplasia were also associated with increased risk of DED. The age-standardized prevalence of DED was 4.34%, or 1.68 million men 50 years and older, and is expected to affect more than 2.79 million US men by 2030. Dry eye disease is prevalent and increases with age, hypertension, benign prostatic hyperplasia, and antidepressant use.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Int Rev Immunol
                Journal ID (iso-abbrev): Int. Rev. Immunol
                Journal ID (publisher-id): IRI
                Title: International Reviews of Immunology
                Publisher: Informa Healthcare
                ISSN (Print): 0883-0185
                ISSN (Electronic): 1563-5244
                Publication date (Print): 13 February 2013
                Publication date (Electronic): 29 January 2013
                Volume: 32
                Issue: 1
                Pages: 19-41
                Affiliations
                Biological Sciences, Inflammation Research Program, Allergan Inc. , Irvine, CA, USA
                Ocular Surface Center, Cullen Eye Institute, Baylor College of Medicine , Houston, TX, USA
                Author notes
                Address correspondence to Michael E. Stern, Biological Sciences, Inflammation Research Program, Allergan Inc. , 2525 Dupont Drive, RD3-2D, Irvine, CA 92612, USA. Email: stern_michael@ 123456allergan.com
                Article
                Publisher ID: IRI_A_748052_O
                DOI: 10.3109/08830185.2012.748052
                PMC ID: 3587314
                PubMed ID: 23360156
                SO-VID: c0823cec-4b7d-44e8-93b4-b970d9385c1c
                Copyright © © 2013 Informa Healthcare USA, Inc.
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the source is credited.

                History
                Categories
                Subject: Immunology of the Eye - Inside and Out

                Keywords: autoimmunity,dry eye,inflammation,lacrimal functional unit,sjögren's syndrome,t cell
                Data availability:
                Keywords: autoimmunity, dry eye, inflammation, lacrimal functional unit, sjögren's syndrome, t cell

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