Comparative Analysis of Age-Related Changes in Lacrimal Glands and Meibomian Glands of a C57BL/6 Male Mouse Model

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Abstract

It is not known how biological changes in the lacrimal (LGs) and meibomian (MGs) glands contribute to dry eye disease (DED) in a time-dependent manner. In this study, we investigated time-sequenced changes in the inflammation, oxidative stress, and senescence of stem cells in both glands of an aging-related DED mouse model. Eight-week (8W)-, one-year (1Y)-, and two-year (2Y)-old C57BL/6 male mice were used. MG areas of the upper and lower eyelids were analyzed by transillumination meibography imaging. The number of CD45 ⁺, 8-OHdG ⁺, Ki-67 ⁺, and BrdU ⁺ cells was compared in both glands. Increased corneal staining and decreased tear secretion were observed in aged mice. The MG dropout area increased with aging, and the age-adjusted MG area in lower lids was negatively correlated with the National Eye Institute (NEI) score. Increased CD4 ⁺ interferon (IFN)-γ ⁺ cells in LGs were found in both aged mice. An increase in 8-OHdG ⁺ cells in both glands was evident in 2Y-old mice. Reduced Ki-67 ⁺ cells, but no change in CD45 ⁺ cells, was observed in the MGs of 1Y-old mice. Increased BrdU ⁺ cells were observed in the LGs of aged mice. This suggests that age-dependent DED in C57BL/6 mice is related to inflammation of the LGs, the development of MG atrophy, and oxidative stress in both glands.

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PPAR gamma is required for the differentiation of adipose tissue in vivo and in vitro.

E D Rosen, P Sarraf, A E Troy … (1999)

The process of adipogenesis is known to involve the interplay of several transcription factors. Activation of one of these factors, the nuclear hormone receptor PPAR gamma, is known to promote fat cell differentiation in vitro. Whether PPAR gamma is required for this process in vivo has remained an open question because a viable loss-of-function model for PPAR gamma has been lacking. We demonstrate here that mice chimeric for wild-type and PPAR gamma null cells show little or no contribution of null cells to adipose tissue, whereas most other organs examined do not require PPAR gamma for proper development. In vitro, the differentiation of ES cells into fat is shown to be dependent on PPAR gamma gene dosage. These data provide direct evidence that PPAR gamma is essential for the formation of fat.

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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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The Th17/Treg balance is disturbed during aging.

Vanessa Schmitt, Lothar Rink, Peter Uciechowski (2013)

Aging is associated with multiple changes in the proliferative and functional abilities of the immune system which are not related to any pathology but consequences in immunosenescence and inflammaging. T helper (TH) 17 cells have been implicated in the development of autoimmune and chronic inflammatory diseases in humans. Additionally, a reciprocal relationship between these pro-inflammatory TH17 and the anti-inflammatory regulatory T cells (Tregs) has been described. Recent studies reported an increase of TH17 cells in aged humans and aged mice, but the role of TH17 cells and their relation to Tregs is poorly understood in human aging. This study investigated the proportion of TH17 (CD4+ IL23 receptor(R)+) cells and Tregs (CD4+ Foxp3+) as well as Interleukin (IL)-17 and IL-10 production in four different age groups from human healthy donors. The data revealed a continual increase of basal CD4+ IL23R+ cell amounts in the different age groups. By analyzing the balance of both T-cell subsets it was observed that, on a basal resting level, TH17 cells were significantly increased in older individuals whereas Tregs were reduced. However, the TH17/Treg ratio decreased age-dependently after stimulation and was accompanied by elevated Foxp3 mRNA and IL-10 protein expressions. In conclusion, changes of the TH17/Treg ratios in combination with altered cytokine expression during aging may contribute to an imbalance between the pro-inflammatory and the anti-inflammatory immune response. This indicates a higher susceptibility to develop inflammatory diseases with increasing age.

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Author and article information

Journal

Journal ID (nlm-ta): Int J Mol Sci

Journal ID (iso-abbrev): Int J Mol Sci

Journal ID (publisher-id): ijms

Title: International Journal of Molecular Sciences

Publisher: MDPI

ISSN (Electronic): 1422-0067

Publication date (Electronic): 11 June 2020

Publication date Collection: June 2020

Volume: 21

Issue: 11

Electronic Location Identifier: 4169

Affiliations

[1 ]Department of Ophthalmology, Seoul National University College of Medicine, Seoul 03080, Korea; ifree7@ 123456gmail.com

[2 ]Laboratory of Ocular Regenerative Medicine and Immunology, Seoul Artificial Eye Center, Seoul National University Hospital Biomedical Research Institute, Seoul 03080, Korea; enter2357@ 123456naver.com

[3 ]Department of Ophthalmology, Seoul National University Hospital, Seoul 03080, Korea

[4 ]Department of Ophthalmology, College of Medicine, The Catholic University of Korea, Seoul 07345, Korea

Author notes

[* ]Correspondence: huanghs@ 123456hanmail.net (H.S.H.); kmk9@ 123456snu.ac.kr (M.K.K.); Tel.: +82-2-3779-1025 (H.S.H.); +82-2-2072-2665 (M.K.K.); Fax: +82-2-761-6869 (H.S.H.); +82-2-741-3187 (M.K.K.)

[†]

These authors contributed equally to this work.

Author information

Chang Ho Yoon https://orcid.org/0000-0003-2203-5709

Mee Kum Kim https://orcid.org/0000-0001-7850-6894

Article

Publisher ID: ijms-21-04169

DOI: 10.3390/ijms21114169

PMC ID: 7313015

PubMed ID: 32545199

SO-VID: 8ebec953-b6e6-4e31-baf7-7458b9774493

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Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

Comparative Analysis of Age-Related Changes in Lacrimal Glands and Meibomian Glands of a C57BL/6 Male Mouse Model

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Stress signalling in stem cells

Most cited references 43

PPAR gamma is required for the differentiation of adipose tissue in vivo and in vitro.

Prevalence of dry eye syndrome among US women.

The Th17/Treg balance is disturbed during aging.

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