Aged Mice Devoid of the M<sub>3</sub> Muscarinic Acetylcholine Receptor Develop Mild Dry Eye Disease
The parasympathetic nervous system is critically involved in the regulation of tear secretion by activating muscarinic acetylcholine receptors. Hence, various animal models targeting parasympathetic signaling have been developed to induce dry eye disease (DED). However, the muscarinic receptor subty...
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MDPI AG
2021-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/11/6133 |
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| author | Aytan Musayeva Subao Jiang Yue Ruan Jenia Kouchek Zadeh Panagiotis Chronopoulos Norbert Pfeiffer Werner E.G. Müller Maximilian Ackermann Ning Xia Huige Li Adrian Gericke |
| author_facet | Aytan Musayeva Subao Jiang Yue Ruan Jenia Kouchek Zadeh Panagiotis Chronopoulos Norbert Pfeiffer Werner E.G. Müller Maximilian Ackermann Ning Xia Huige Li Adrian Gericke |
| author_sort | Aytan Musayeva |
| collection | DOAJ |
| description | The parasympathetic nervous system is critically involved in the regulation of tear secretion by activating muscarinic acetylcholine receptors. Hence, various animal models targeting parasympathetic signaling have been developed to induce dry eye disease (DED). However, the muscarinic receptor subtype (M<sub>1</sub>–M<sub>5</sub>) mediating tear secretion remains to be determined. This study was conducted to test the hypothesis that the M<sub>3</sub> receptor subtype regulates tear secretion and to evaluate the ocular surface phenotype of mice with targeted disruption of the M<sub>3</sub> receptor (M3R<sup>−/−</sup>). The experimental techniques included quantification of tear production, fluorescein staining of the ocular surface, environmental scanning electron microscopy, assessment of proliferating cells in the corneal epithelium and of goblet cells in the conjunctiva, quantification of mRNA for inflammatory cytokines and prooxidant redox enzymes and quantification of reactive oxygen species. Tear volume was reduced in M3R<sup>−/−</sup> mice compared to age-matched controls at the age of 3 months and 15 months, respectively. This was associated with mild corneal epitheliopathy in the 15-month-old but not in the 3-month-old M3R<sup>−/−</sup> mice. M3R<sup>−/−</sup> mice at the age of 15 months also displayed changes in corneal epithelial cell texture, reduced conjunctival goblet cell density, oxidative stress and elevated mRNA expression levels for inflammatory cytokines and prooxidant redox enzymes. The findings suggest that the M<sub>3</sub> receptor plays a pivotal role in tear production and its absence leads to ocular surface changes typical for DED at advanced age. |
| first_indexed | 2024-03-10T10:39:00Z |
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| language | English |
| last_indexed | 2024-03-10T10:39:00Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-59f0a99c96f34bc69b04ecce019905cd2023-11-21T23:03:36ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-06-012211613310.3390/ijms22116133Aged Mice Devoid of the M<sub>3</sub> Muscarinic Acetylcholine Receptor Develop Mild Dry Eye DiseaseAytan Musayeva0Subao Jiang1Yue Ruan2Jenia Kouchek Zadeh3Panagiotis Chronopoulos4Norbert Pfeiffer5Werner E.G. Müller6Maximilian Ackermann7Ning Xia8Huige Li9Adrian Gericke10Department of Ophthalmology, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131 Mainz, GermanyDepartment of Ophthalmology, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131 Mainz, GermanyDepartment of Ophthalmology, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131 Mainz, GermanyDepartment of Ophthalmology, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131 Mainz, GermanyDepartment of Ophthalmology, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131 Mainz, GermanyDepartment of Ophthalmology, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131 Mainz, GermanyERC Advanced Investigator Grant Research Group at the Institute for Physiological Chemistry, University Medical Center, Johannes Gutenberg University Mainz, Duesbergweg 6, 55128 Mainz, GermanyInstitute of Functional and Clinical Anatomy, University Medical Center, Johannes Gutenberg University Mainz, Johann-Joachim-Becher-Weg 13, 55128 Mainz, GermanyDepartment of Pharmacology, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131 Mainz, GermanyDepartment of Pharmacology, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131 Mainz, GermanyDepartment of Ophthalmology, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131 Mainz, GermanyThe parasympathetic nervous system is critically involved in the regulation of tear secretion by activating muscarinic acetylcholine receptors. Hence, various animal models targeting parasympathetic signaling have been developed to induce dry eye disease (DED). However, the muscarinic receptor subtype (M<sub>1</sub>–M<sub>5</sub>) mediating tear secretion remains to be determined. This study was conducted to test the hypothesis that the M<sub>3</sub> receptor subtype regulates tear secretion and to evaluate the ocular surface phenotype of mice with targeted disruption of the M<sub>3</sub> receptor (M3R<sup>−/−</sup>). The experimental techniques included quantification of tear production, fluorescein staining of the ocular surface, environmental scanning electron microscopy, assessment of proliferating cells in the corneal epithelium and of goblet cells in the conjunctiva, quantification of mRNA for inflammatory cytokines and prooxidant redox enzymes and quantification of reactive oxygen species. Tear volume was reduced in M3R<sup>−/−</sup> mice compared to age-matched controls at the age of 3 months and 15 months, respectively. This was associated with mild corneal epitheliopathy in the 15-month-old but not in the 3-month-old M3R<sup>−/−</sup> mice. M3R<sup>−/−</sup> mice at the age of 15 months also displayed changes in corneal epithelial cell texture, reduced conjunctival goblet cell density, oxidative stress and elevated mRNA expression levels for inflammatory cytokines and prooxidant redox enzymes. The findings suggest that the M<sub>3</sub> receptor plays a pivotal role in tear production and its absence leads to ocular surface changes typical for DED at advanced age.https://www.mdpi.com/1422-0067/22/11/6133corneadry eye diseaseM<sub>3</sub>muscarinic receptortear secretion |
| spellingShingle | Aytan Musayeva Subao Jiang Yue Ruan Jenia Kouchek Zadeh Panagiotis Chronopoulos Norbert Pfeiffer Werner E.G. Müller Maximilian Ackermann Ning Xia Huige Li Adrian Gericke Aged Mice Devoid of the M<sub>3</sub> Muscarinic Acetylcholine Receptor Develop Mild Dry Eye Disease International Journal of Molecular Sciences cornea dry eye disease M<sub>3</sub> muscarinic receptor tear secretion |
| title | Aged Mice Devoid of the M<sub>3</sub> Muscarinic Acetylcholine Receptor Develop Mild Dry Eye Disease |
| title_full | Aged Mice Devoid of the M<sub>3</sub> Muscarinic Acetylcholine Receptor Develop Mild Dry Eye Disease |
| title_fullStr | Aged Mice Devoid of the M<sub>3</sub> Muscarinic Acetylcholine Receptor Develop Mild Dry Eye Disease |
| title_full_unstemmed | Aged Mice Devoid of the M<sub>3</sub> Muscarinic Acetylcholine Receptor Develop Mild Dry Eye Disease |
| title_short | Aged Mice Devoid of the M<sub>3</sub> Muscarinic Acetylcholine Receptor Develop Mild Dry Eye Disease |
| title_sort | aged mice devoid of the m sub 3 sub muscarinic acetylcholine receptor develop mild dry eye disease |
| topic | cornea dry eye disease M<sub>3</sub> muscarinic receptor tear secretion |
| url | https://www.mdpi.com/1422-0067/22/11/6133 |
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