July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Atrophy and Impaired Contraction of the Myoepithelial Cells in Lacrimal Glands of Sjögren’s Syndrome Animal Models of Dry Eye Disease
Author Affiliations & Notes
  • Driss Zoukhri
    Comprehensive Care, Tufts University School of Dental Medicine, Boston, Massachusetts, United States
    Ophthalmology, Tufts University School of Medicine, Boston, Massachusetts, United States
  • Dillon Hawley
    Comprehensive Care, Tufts University School of Dental Medicine, Boston, Massachusetts, United States
  • Xin Tang
    Molecular Medicine, The Scripps Research Institution, La Jolla, California, United States
  • Tatiana Zyrianova
    Molecular Medicine, The Scripps Research Institution, La Jolla, California, United States
  • Mihir Shah
    Ophthalmology, USC Roski Eye Institute, Keck School of Medicine of University of Southern California, Los Angelos, California, United States
  • Srikanth Reddy Janga
    Ophthalmology, USC Roski Eye Institute, Keck School of Medicine of University of Southern California, Los Angelos, California, United States
  • Alexandra Letourneau
    Comprehensive Care, Tufts University School of Dental Medicine, Boston, Massachusetts, United States
  • Martin Schicht
    Anatomy II, Friedrich Alexander University Erlangen-Nürnberg, Erlangen, Germany
  • Friedrich P Paulsen
    Anatomy II, Friedrich Alexander University Erlangen-Nürnberg, Erlangen, Germany
  • Sarah Hamm-Alvarez
    Ophthalmology, USC Roski Eye Institute, Keck School of Medicine of University of Southern California, Los Angelos, California, United States
    University of Southern California School of Pharmacy, Los Angelos, California, United States
  • Helen P Makarenkova
    Molecular Medicine, The Scripps Research Institution, La Jolla, California, United States
  • Footnotes
    Commercial Relationships   Driss Zoukhri, None; Dillon Hawley, None; Xin Tang, None; Tatiana Zyrianova, None; Mihir Shah, None; Srikanth Janga, None; Alexandra Letourneau, None; Martin Schicht, None; Friedrich Paulsen, None; Sarah Hamm-Alvarez, None; Helen Makarenkova, None
  • Footnotes
    Support  NIH Grants: EY012383 and EY026202
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 2286. doi:
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    • Get Citation

      Driss Zoukhri, Dillon Hawley, Xin Tang, Tatiana Zyrianova, Mihir Shah, Srikanth Reddy Janga, Alexandra Letourneau, Martin Schicht, Friedrich P Paulsen, Sarah Hamm-Alvarez, Helen P Makarenkova; Atrophy and Impaired Contraction of the Myoepithelial Cells in Lacrimal Glands of Sjögren’s Syndrome Animal Models of Dry Eye Disease
      . Invest. Ophthalmol. Vis. Sci. 2018;59(9):2286.

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

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Abstract

Purpose : The lacrimal gland (LG) secretory units are made up of acini and myoepithelial cells (MECs), which are able to contract to expel fluid and proteins from the acini. MECs also synthetize basement membrane and secrete growth factors. The impact of chronic inflammation on MECs function is not known; therefore, we used two well-studied animal models of human Sjögren’s syndrome, NOD and MRL/lpr mice, to investigate the effect of inflammation on MECs morphology and contraction.

Methods : MECs size was calculated on a-smooth muscle actin (SMA) stained LG sections, using ImageJ software. The amounts of myofilament proteins (SMA, calponin, and caldesmon) were determined by Western blotting. RT-PCR, Western blotting and immunohistochemical experiments were used to investigate the presence and expression of oxytocin receptors (a hormone known to induce mammary gland MECs contraction). Finally, MECs contraction in response to oxytocin stimulation was determined using confocal microscopy.

Results : Our immunohistochemical studies showed that compared to control animals; there was a statistically significant reduction in MEC size in NOD and MRL/lpr LGs. MECs from diseased LGs had significantly shorter cell processes compared to control mice and a significant reduction of general cell size. Western blotting data showed a statistically significant decrease in the amount of SMA and calponin proteins in NOD LGs when compared to control BALB/c mice. Moreover, we confirmed the presence of oxytocin receptors in the murine and human MECs. In response to oxytocin stimulation, acini areas and diameters were significantly reduced in LGs from BALB/c mice whereas those from NOD mice LGs did not. Furthermore, in unstimulated tissues, we found that acinar areas were significantly bigger in NOD versus BALB/c mice LGs.

Conclusions : We conclude that chronic inflammation of the LG first leads to atrophy of the MECs and decreased expression of myofilament proteins, which leads to impaired contraction and ultimately, impaired fluid and protein secretion from the acinar cells. MECs atrophy will also result in aberrant basement membrane secretion, leading to dysfunction of the whole LG secretory unit.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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