June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
Accelerated Aging in the Lacrimal Glands of Estrogen-deficient Aromatase (Aro) and Estrogen Receptor (ER) Knockout Mice
Author Affiliations & Notes
  • Yichen Bai
    Ophthalmology, Southern Medical University, Guangzhou, Guangdong, China
    Ophthalmology, University of Missouri, Columbia, Missouri, United States
  • Xiaowei Yang
    State Key Laborary of Ophthalmology, Sun Yat-Sen University Zhongshan Ophthalmic Center, Guangzhou, Guangdong, China
    Ophthalmology, University of Missouri, Columbia, Missouri, United States
  • Xiaohe Lu
    Ophthalmology, Southern Medical University, Guangzhou, Guangdong, China
  • Xingwu Zhong
    State Key Laborary of Ophthalmology, Sun Yat-Sen University Zhongshan Ophthalmic Center, Guangzhou, Guangdong, China
  • Dennis Lubahn
    Biochemistry, University of Missouri, Columbia, Missouri, United States
  • Lixing W Reneker
    Ophthalmology, University of Missouri, Columbia, Missouri, United States
  • Footnotes
    Commercial Relationships   Yichen Bai, None; Xiaowei Yang, None; Xiaohe Lu, None; Xingwu Zhong, None; Dennis Lubahn, None; Lixing Reneker, None
  • Footnotes
    Support  University of Missouri Research Council fund, NIH grant EY029106
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 707. doi:
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      Yichen Bai, Xiaowei Yang, Xiaohe Lu, Xingwu Zhong, Dennis Lubahn, Lixing W Reneker; Accelerated Aging in the Lacrimal Glands of Estrogen-deficient Aromatase (Aro) and Estrogen Receptor (ER) Knockout Mice. Invest. Ophthalmol. Vis. Sci. 2021;62(8):707.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : The risk of dry eye disease (DED) increases with age in both men and women. Although sex hormones are known to be important for maintaining the ocular surface health, their role in the etiology of DED is still undefined. In this study, age-related changes were investigated in the ocular surface tissues of aromatase (Aro) and estrogen receptor (ER) KO mice.

Methods : The pathology of ocular surface tissues in the aromatase (an estrogen synthase) and estrogen receptor isoform, ERα and ERβ, knockout (KO) mice was investαigated. The age-related changes in the KO mice were compared to their age- and sex-matched wild type (WT) control mice.

Results : In 6-month old male Aro-KO mice, estrogen deficiency resulted in multiple defects in the lacrimal glands, which can be best characterized as accelerated aging, those including severe acinar atrophy, appearance of Harderian gland-like structures, increase of gland ducts and morphologic dysplasia (cytomegaly, karyomegaly, and cell and nuclear polymorphism) across the gland. Interestingly, the similar phenotype was also seen in the male ERα KO mice as young as 4-month old, suggesting that estrogen's anti-aging effect in the lacrimal gland of male mice is likely mediated through ERα pathway. Deletion of aramatase significantly increased the size and weight of the lacrimal glands in female KO mice. Increase of immune cell infiltration was found in the lacrimal glands of female Aro-KO mice when compared to the age-matched female WT mice. No apparent histopathology was noticed in the meibomian glands and goblet cells between the Aro-KO and WT mice. No significant difference was found in the corneal fluorescein staining score between the one-year old Aro-KO mice and their age- and sex-matched WT control mice.

Conclusions : Estrogen deficiency results in different responses in the lacrimal glands of male and female mice. Our study suggests that estrogen can play an anti-aging role, mediated through ERα, in the lacrimal glands of male mice. The anti-inflammatory function mediated via the estrogen-ERβ pathway in female lacrimal glands is under further investigation.

This is a 2021 ARVO Annual Meeting abstract.

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