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Detection of intrinsic cholinergic system in the human lacrimal drainage system: evidence and potential implications

  • Basic Science
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Abstract

Purpose

To investigate the presence and distribution of epithelial and non-epithelial cholinergic system and cholinergic brush cells in the human lacrimal drainage system.

Methods

The study was performed on fresh frozen human cadaveric samples of the lacrimal drainage system. Immunohistochemistry was performed for assessing the presence and distribution of cholinergic brush cell proteins—villin, acetylcholine synthesizing enzyme, choline acetyltransferase (ChAT); vesicular acetylcholine transporter (VAChT); components of canonical taste transduction signaling cascade, phospholipase C β2 (PLCβ2), and transient receptor potential cation channel, subfamily M, and member 5 (TRPM5). In addition, immunoreactivity to carbonic anhydrase 4 (CA4) was assessed. The immunoreactivity was scored as positive or negative and the distribution patterns in the canaliculi, lacrimal sac, and nasolacrimal duct were investigated. In addition, ultrastructural analysis was performed to ascertain the presence of brush cells by means of scanning electron microscopy (SEM).

Results

Villin revealed immunoreactivity in the superficial epithelial cells of lacrimal sac and nasolacrimal ducts. Positive immunoreactivity was also found for ChAT, VAChT, TRPM5, and PLCβ2. ChAT expression was limited to the superficial epithelial layers of the lacrimal sac epithelium. TRPM5 and PLCβ2 were expressed on the cell membranes, cytoplasm, and basolateral surfaces of the lacrimal sac epithelium and also showed strong expression in the submucosal glandular acinar cells. VAChT showed strong expression in the canaliculus and lacrimal sac and was expressed on the surface of the superficial epithelial cells and the submucosal glandular acinar cells and lining of the blood vessels. There was a uniformly negative immunoreactivity for CA4. SEM revealed single epithelial cells with dense tuft of rigid apical microvilli in the lacrimal sac and nasolacrimal ducts.

Conclusions

This study provides a proof of principle for the presence of an intrinsic epithelial cholinergic mechanism in the lacrimal drainage system.

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Acknowledgements

The authors wish to acknowledge Ms. Hong Nguyen for her technical help with immunohistochemistry.

Funding

Alexander Von Humboldt provided financial support to Dr. Ali in the form of stipend to support stay and research endeavors in Germany. Friedrich Paulsen was supported by Deutsche Forschungsgemeinschaft (DFG) grants PA738/1-1 to 1-5 as well as PA738/2-1 as research funding. The sponsors had no role in design or conduct of this research.

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Authors and Affiliations

  1. Institute of Anatomy II, Friedrich-Alexander University, Erlangen-Nürnberg, Germany

    Mohammad Javed Ali, Mareile Glóckner, Lars Bräuer & Friedrich Paulsen

  2. Govindram Seksaria Institute of Dacryology, L.V.Prasad Eye Institute, Hyderabad, India

    Mohammad Javed Ali, Mareile Glóckner, Martin Schicht, Lars Bräuer & Friedrich Paulsen

Authors
  1. Mohammad Javed Ali
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  2. Mareile Glóckner
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  3. Martin Schicht
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  4. Lars Bräuer
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  5. Friedrich Paulsen
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Corresponding author

Correspondence to Friedrich Paulsen.

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Conflict of interest

All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria, educational grants, participation in speakers’ bureaus, membership, employment, consultancies, stock ownership, other equity interest, and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.

Animal experiments

This article does not contain any studies with animals performed by any of the authors.

Financial disclosure

Mohammad Javed Ali received support from the Alexander von Humboldt Foundation for his research and he also receives royalties from Springer for the textbook “Principles and Practice of Lacrimal Surgery” and treatise “Atlas of Lacrimal Drainage Disorders”. Friedrich Paulsen was supported by Deutsche Forschungsgemeinschaft (DFG) grants PA738/1-1 to 1-5 as well as PA738/2-1. He receives royalties from Elsevier for the anatomy atlas “Sobotta” and the Sobotta Anatomy Textbook. The present work was performed in fulfillment of the requirements for obtaining the degree Dr. med. dent (MG).

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Ali, M.J., Glóckner, M., Schicht, M. et al. Detection of intrinsic cholinergic system in the human lacrimal drainage system: evidence and potential implications. Graefes Arch Clin Exp Ophthalmol 256, 2097–2102 (2018). https://doi.org/10.1007/s00417-018-4124-4

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  • DOI: https://doi.org/10.1007/s00417-018-4124-4

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