Novel alterations in corneal neuroimmune phenotypes in mice with central nervous system tauopathy
Abstract Background Tauopathy in the central nervous system (CNS) is a histopathological hallmark of frontotemporal dementia (FTD) and Alzheimer’s disease (AD). Although AD is accompanied by various ocular changes, the effects of tauopathy on the integrity of the cornea, which is densely innervated...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-04-01
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| Series: | Journal of Neuroinflammation |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12974-020-01803-7 |
| _version_ | 1811220962398437376 |
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| author | Haihan Jiao Laura E. Downie Xin Huang Mengliang Wu Sara Oberrauch Ryan J. Keenan Laura H. Jacobson Holly R. Chinnery |
| author_facet | Haihan Jiao Laura E. Downie Xin Huang Mengliang Wu Sara Oberrauch Ryan J. Keenan Laura H. Jacobson Holly R. Chinnery |
| author_sort | Haihan Jiao |
| collection | DOAJ |
| description | Abstract Background Tauopathy in the central nervous system (CNS) is a histopathological hallmark of frontotemporal dementia (FTD) and Alzheimer’s disease (AD). Although AD is accompanied by various ocular changes, the effects of tauopathy on the integrity of the cornea, which is densely innervated by the peripheral nervous system and is populated by resident dendritic cells, is still unknown. The aim of this study was to investigate if neuroimmune interactions in the cornea are affected by CNS tauopathy. Methods Corneas from wild type (WT) and transgenic rTg4510 mice that express the P301L tau mutation were examined at 2, 6, 8, and 11 months. Clinical assessment of the anterior segment of the eye was performed using spectral domain optical coherence tomography. The density of the corneal epithelial sensory nerves and the number and field area of resident epithelial dendritic cells were assessed using immunofluorescence. The immunological activation state of corneal and splenic dendritic cells was examined using flow cytometry and compared between the two genotypes at 9 months of age. Results Compared to age-matched WT mice, rTg4510 mice had a significantly lower density of corneal nerve axons at both 8 and 11 months of age. Corneal nerves in rTg4510 mice also displayed a higher percentage of beaded nerve axons and a lower density of epithelial dendritic cells compared to WT mice. From 6 months of age, the size of the corneal dendritic cells was significantly smaller in rTg4510 compared to WT mice. Phenotypic characterization by flow cytometry demonstrated an activated state of dendritic cells (CD86+ and CD45+ CD11b+CD11c+) in the corneas of rTg4510 compared to WT mice, with no distinct changes in the spleen monocytes/dendritic cells. At 2 months of age, there were no significant differences in the neural or immune structures between the two genotypes. Conclusions Corneal sensory nerves and epithelial dendritic cells were altered in the rTg4510 mouse model of tauopathy, with temporal changes observed with aging. The activation of corneal dendritic cells prior to the gradual loss of neighboring sensory nerves suggests an early involvement of corneal immune cells in tau-associated pathology originating in the CNS. |
| first_indexed | 2024-04-12T07:51:47Z |
| format | Article |
| id | doaj.art-f8b031e4e4be4a85a5101403a03da0a7 |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-04-12T07:51:47Z |
| publishDate | 2020-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj.art-f8b031e4e4be4a85a5101403a03da0a72022-12-22T03:41:35ZengBMCJournal of Neuroinflammation1742-20942020-04-0117111510.1186/s12974-020-01803-7Novel alterations in corneal neuroimmune phenotypes in mice with central nervous system tauopathyHaihan Jiao0Laura E. Downie1Xin Huang2Mengliang Wu3Sara Oberrauch4Ryan J. Keenan5Laura H. Jacobson6Holly R. Chinnery7Department of Optometry and Vision Sciences, The University of MelbourneDepartment of Optometry and Vision Sciences, The University of MelbourneInnate Phagocytosis Laboratory, Florey Institute of Neuroscience and Mental HealthDepartment of Optometry and Vision Sciences, The University of MelbourneDepartment of Pharmacology and Therapeutics, The University of MelbourneDepartment of Pharmacology and Therapeutics, The University of MelbourneDepartment of Pharmacology and Therapeutics, The University of MelbourneDepartment of Optometry and Vision Sciences, The University of MelbourneAbstract Background Tauopathy in the central nervous system (CNS) is a histopathological hallmark of frontotemporal dementia (FTD) and Alzheimer’s disease (AD). Although AD is accompanied by various ocular changes, the effects of tauopathy on the integrity of the cornea, which is densely innervated by the peripheral nervous system and is populated by resident dendritic cells, is still unknown. The aim of this study was to investigate if neuroimmune interactions in the cornea are affected by CNS tauopathy. Methods Corneas from wild type (WT) and transgenic rTg4510 mice that express the P301L tau mutation were examined at 2, 6, 8, and 11 months. Clinical assessment of the anterior segment of the eye was performed using spectral domain optical coherence tomography. The density of the corneal epithelial sensory nerves and the number and field area of resident epithelial dendritic cells were assessed using immunofluorescence. The immunological activation state of corneal and splenic dendritic cells was examined using flow cytometry and compared between the two genotypes at 9 months of age. Results Compared to age-matched WT mice, rTg4510 mice had a significantly lower density of corneal nerve axons at both 8 and 11 months of age. Corneal nerves in rTg4510 mice also displayed a higher percentage of beaded nerve axons and a lower density of epithelial dendritic cells compared to WT mice. From 6 months of age, the size of the corneal dendritic cells was significantly smaller in rTg4510 compared to WT mice. Phenotypic characterization by flow cytometry demonstrated an activated state of dendritic cells (CD86+ and CD45+ CD11b+CD11c+) in the corneas of rTg4510 compared to WT mice, with no distinct changes in the spleen monocytes/dendritic cells. At 2 months of age, there were no significant differences in the neural or immune structures between the two genotypes. Conclusions Corneal sensory nerves and epithelial dendritic cells were altered in the rTg4510 mouse model of tauopathy, with temporal changes observed with aging. The activation of corneal dendritic cells prior to the gradual loss of neighboring sensory nerves suggests an early involvement of corneal immune cells in tau-associated pathology originating in the CNS.http://link.springer.com/article/10.1186/s12974-020-01803-7Central nervous system tauopathyImmune cellsCorneaSensory nervesPeripheral nervous system |
| spellingShingle | Haihan Jiao Laura E. Downie Xin Huang Mengliang Wu Sara Oberrauch Ryan J. Keenan Laura H. Jacobson Holly R. Chinnery Novel alterations in corneal neuroimmune phenotypes in mice with central nervous system tauopathy Journal of Neuroinflammation Central nervous system tauopathy Immune cells Cornea Sensory nerves Peripheral nervous system |
| title | Novel alterations in corneal neuroimmune phenotypes in mice with central nervous system tauopathy |
| title_full | Novel alterations in corneal neuroimmune phenotypes in mice with central nervous system tauopathy |
| title_fullStr | Novel alterations in corneal neuroimmune phenotypes in mice with central nervous system tauopathy |
| title_full_unstemmed | Novel alterations in corneal neuroimmune phenotypes in mice with central nervous system tauopathy |
| title_short | Novel alterations in corneal neuroimmune phenotypes in mice with central nervous system tauopathy |
| title_sort | novel alterations in corneal neuroimmune phenotypes in mice with central nervous system tauopathy |
| topic | Central nervous system tauopathy Immune cells Cornea Sensory nerves Peripheral nervous system |
| url | http://link.springer.com/article/10.1186/s12974-020-01803-7 |
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