Skip to main content

Advertisement

Log in

Meibomian gland cells display a differentiation-dependent composition of desmosomes

  • Original Paper
  • Published:
Histochemistry and Cell Biology Aims and scope Submit manuscript

Abstract

Meibomian glands are a modified type of sebaceous glands within the eye lid, which produce an oily secretion important for the stabilization and the prevention of evaporation of the tear film. The holocrine secretory mode of Meibomian glands is characterized by the centripetal movement, the maturation and finally degeneration of the acinar epithelial cells. The process of maturation and degeneration is paralleled by altered expression pattern of certain proteins and the intracellular accumulation of Meibomian gland lipids. In this study, we investigated the correlation between the differentiation status of Meibomian acinus cells and the presence of adhesive junctions. By ultrastructural analyses, we showed for the first time that the frequency of desmosomes increased with the degree of differentiation. Importantly, we detected a differentiation-dependent distribution pattern of desmosomes within the Meibomian gland cells of the acinus, whereas molecules of other cell junctions, e.g., adherens junctions, are equally distributed. Together, these findings provide new insights into the processes of Meibomian gland secretion and may be important for the interpretation of Meibomian gland dysfunction causing diseases like the dry eye syndrome.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Abbreviations

Ab:

Antibody

AJ:

Adherens junction

bc:

Basal cell

bm:

Basement membrane

Ck:

Cytokeratin

Dp:

Desmoplakin

Dsc:

Desmocollin

Dsg:

Desmoglein

E-cad:

E-cadherin

H&E:

Hematoxylin and eosin

HMGEC:

Human Meibomian gland cell line

Mc:

Meibomian gland cells

MGD:

Meibomian gland dysfunction

p38MAPK:

p38 mitogen-activated protein kinase

Pg:

Plakoglobin

TJ:

Tight junction

References

  • Abreu-Velez AM, Howard MS, Hashimoto T, Grossniklaus HE (2010) Human eyelid meibomian glands and tarsal muscle are recognized by autoantibodies from patients affected by a new variant of endemic pemphigus foliaceus in El-Bagre, Colombia, South America. J Am Acad Dermatol 62(3):437–447

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Berkowitz P, Hu P, Warren S, Liu Z, Diaz LA, Rubenstein DS (2006) p38MAPK inhibition prevents disease in pemphigus vulgaris mice. Proc Natl Acad Sci USA 103(34):12855–12860

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bron AJ, Tiffany JM, Gouveia SM, Yokoi N, Voon LW (2004) Functional aspects of the tear film lipid layer. Exp Eye Res 78(3):347–360

    Article  CAS  PubMed  Google Scholar 

  • Butovich IA, Uchiyama E, McCulley JP (2007) Lipids of human meibum: mass-spectrometric analysis and structural elucidation. J Lipid Res 48(10):2220–2235

    Article  CAS  PubMed  Google Scholar 

  • Craig JP, Blades K, Patel S (1995) Tear lipid layer structure and stability following expression of the meibomian glands. Ophthalmic Physiol Opt 15(6):569–574

    Article  CAS  PubMed  Google Scholar 

  • Gorgas K, Volkl A (1984) Peroxisomes in sebaceous glands. IV. Aggregates of tubular peroxisomes in the mouse Meibomian gland. Histochem J 16(10):1079–1098

    Article  CAS  PubMed  Google Scholar 

  • Hampel U, Schroder A, Mitchell T, Brown S, Snikeris P, Garreis F, Kunnen C, Willcox M, Paulsen F (2015) Serum-induced keratinization processes in an immortalized human meibomian gland epithelial cell line. PLoS ONE 10(6):e0128096

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Heupel WM, Zillikens D, Drenckhahn D, Waschke J (2008) Pemphigus vulgaris IgG directly inhibit desmoglein 3-mediated transinteraction. J Immunol 181(3):1825–1834

    Article  CAS  PubMed  Google Scholar 

  • Jester JV, Nicolaides N, Smith RE (1981) Meibomian gland studies: histologic and ultrastructural investigations. Invest Ophthalmol Vis Sci 20(4):537–547

    CAS  PubMed  Google Scholar 

  • Kitajima Y (2014) 150 anniversary series: desmosomes and autoimmune disease, perspective of dynamic desmosome remodeling and its impairments in pemphigus. Cell Commun Adhes 1–12

  • Knop E, Knop N, Millar T, Obata H, Sullivan DA (2011) The international workshop on meibomian gland dysfunction: report of the subcommittee on anatomy, physiology, and pathophysiology of the meibomian gland. Invest Ophthalmol Vis Sci 52(4):1938–1978

    Article  PubMed  PubMed Central  Google Scholar 

  • Liu S, Li J, Tan DT, Beuerman RW (2007) The eyelid margin: a transitional zone for 2 epithelial phenotypes. Arch Ophthalmol 125(4):523–532

    Article  CAS  PubMed  Google Scholar 

  • McCulley JP, Shine WE (2003) Meibomian gland function and the tear lipid layer. Ocul Surf 1(3):97–106

    Article  PubMed  Google Scholar 

  • Moll R, Divo M, Langbein L (2008) The human keratins: biology and pathology. Histochem Cell Biol 129(6):705–733

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nelson JD, Shimazaki J, Benitez-del-Castillo JM, Craig JP, McCulley JP, Den S, Foulks GN (2011) The international workshop on meibomian gland dysfunction: report of the definition and classification subcommittee. Invest Ophthalmol Vis Sci 52(4):1930–1937

    Article  PubMed  PubMed Central  Google Scholar 

  • Nichols KK, Foulks GN, Bron AJ, Glasgow BJ, Dogru M, Tsubota K, Lemp MA, Sullivan DA (2011) The international workshop on meibomian gland dysfunction: executive summary. Invest Ophthalmol Vis Sci 52(4):1922–1929

    Article  PubMed  PubMed Central  Google Scholar 

  • Nicolaides N, Kaitaranta JK, Rawdah TN, Macy JI, Boswell FM 3rd, Smith RE (1981) Meibomian gland studies: comparison of steer and human lipids. Invest Ophthalmol Vis Sci 20(4):522–536

    CAS  PubMed  Google Scholar 

  • Olami Y, Zajicek G, Cogan M, Gnessin H, Pe’er J (2001) Turnover and migration of meibomian gland cells in rats’ eyelids. Ophthalmic Res 33(3):170–175

    Article  CAS  PubMed  Google Scholar 

  • Parfitt GJ, Xie Y, Geyfman M, Brown DJ, Jester JV (2013) Absence of ductal hyper-keratinization in mouse age-related meibomian gland dysfunction (ARMGD). Aging 5(11):825–834

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pucker AD, Nichols JJ (2012) Analysis of meibum and tear lipids. Ocul Surf 10(4):230–250

    Article  PubMed  Google Scholar 

  • Reynolds ES (1963) The use of lead citrate at high pH as an electron-opaque stain in electron microscopy. J Cell Biol 17:208–212

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rötzer V, Hartlieb E, Winkler J, Walter E, Schlipp A, Sardy M, Spindler V, Waschke J (2015) Desmoglein 3-dependent signaling regulates keratinocyte migration and wound healing. J Invest Dermatol

  • Schneider MR, Paus R (2010) Sebocytes, multifaceted epithelial cells: lipid production and holocrine secretion. Int J Biochem Cell Biol 42(2):181–185

    Article  CAS  PubMed  Google Scholar 

  • Sirigu P, Shen RL, Pinto da Silva P (1992) Human meibomian glands: the ultrastructure of acinar cells as viewed by thin section and freeze-fracture transmission electron microscopies. Invest Ophthalmol Vis Sci 33(7):2284–2292

    CAS  PubMed  Google Scholar 

  • Spindler V, Rötzer V, Dehner C, Kempf B, Gliem M, Radeva M, Hartlieb E, Harms GS, Schmidt E, Waschke J (2013) Peptide-mediated desmoglein 3 crosslinking prevents pemphigus vulgaris autoantibody-induced skin blistering. J Clin Invest 123(2):800–811

    CAS  PubMed  PubMed Central  Google Scholar 

  • Stanley JR, Amagai M (2006) Pemphigus, bullous impetigo, and the staphylococcal scalded-skin syndrome. N Engl J Med 355(17):1800–1810

    Article  CAS  PubMed  Google Scholar 

  • Tan JC, Tat LT, Francis KB, Mendoza CG, Murrell DF, Coroneo MT (2015) Prospective study of ocular manifestations of pemphigus and bullous pemphigoid identifies a high prevalence of dry eye syndrome. Cornea 34(4):443–448

    Article  PubMed  Google Scholar 

  • Tektas OY, Yadav A, Garreis F, Schlotzer-Schrehardt U, Schicht M, Hampel U, Brauer L, Paulsen F (2012) Characterization of the mucocutaneous junction of the human eyelid margin and meibomian glands with different biomarkers. Ann Anat 194(5):436–445

    Article  CAS  PubMed  Google Scholar 

  • Vielmuth F, Waschke J, Spindler V (2015) Loss of desmoglein binding is not sufficient for keratinocyte dissociation in pemphigus. J Invest Dermatol 135(12):3068–3077

    Article  CAS  PubMed  Google Scholar 

  • Waschke J (2008) The desmosome and pemphigus. Histochem Cell Biol 130(1):21–54

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Waschke J, Spindler V (2014) Desmosomes and extradesmosomal adhesive signaling contacts in pemphigus. Med Res Rev 34:1127–1145

    Article  CAS  PubMed  Google Scholar 

  • Watson ML (1958) Staining of tissue sections for electron microscopy with heavy metals. J Biophys Biochem Cytol 4(4):475–478

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

We thank Prof. Friedrich Paulsen (Friedrich-Alexander University Erlangen Nürnberg) for helpful discussion and Sabine Mühlsimer, Martina Hitzenbichler, Jana Matthes, Axel Unverzagt and Michael Becker for excellent technical assistant.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jens Waschke.

Ethics declarations

Conflict of interest

The authors state no conflict of interest.

Additional information

Dedication to Prof. Dr. Detlev Drenckhahn.

Detlev Drenckhahn is one of the most visionary scientists I have met and worked with. For example, coming from the field of vascular biology he suggested to study desmosomes and to use peptides to modify their adhesion based on the fact that the adhesion molecules of desmosomes belong to the cadherin superfamily similar to the adhesion molecules of endothelial cells. This for us opened up a completely new field of research. Therefore, we contribute this article to this special edition of Histochem Cell Biol in which we characterize the desmosomes of Meibomian glands to lay the ground for a new project on the regulation of cell adhesion in glandular cells.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Rötzer, V., Egu, D. & Waschke, J. Meibomian gland cells display a differentiation-dependent composition of desmosomes. Histochem Cell Biol 146, 685–694 (2016). https://doi.org/10.1007/s00418-016-1475-y

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00418-016-1475-y

Keywords

Navigation