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Intravital Multiphoton Microscopy of the Ocular Surface: Alterations in Conventional Dendritic Cell Morphology and Kinetics in Dry Eye Disease.
- Source :
-
Frontiers in immunology [Front Immunol] 2020 May 07; Vol. 11, pp. 742. Date of Electronic Publication: 2020 May 07 (Print Publication: 2020). - Publication Year :
- 2020
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Abstract
- Dry eye disease (DED) is a multifactorial disease of the ocular surface, characterized by loss of tear film homeostasis and ocular symptoms, in which neurosensory abnormalities have recently been shown to play an etiological role. Although the role of inflammation has been widely studied in DED, the kinetics of immune cells of the ocular surface in this complex disease are hereto unclear. Herein, we utilized intravital multiphoton imaging on transgenic mice to investigate the 3D morphology and kinetics of conventional dendritic cells (cDCs) and the role of ocular surface sensory nerves in regulating them in both the naïve state and experimental DED. Mice with DED had significantly lower tear secretion ( p < 0.01), greater corneal fluorescein staining ( p < 0.001), and higher cDC density in the ocular surface ( p < 0.05), compared to naïve mice. cDCs in DED mice showed morphological alterations in the limbus, exhibiting smaller surface area ( p < 0.001) and volume ( p < 0.001) compared to naïve mice. Furthermore, corneal cDCs showed greater sphericity in DED mice compared to naïve mice ( p < 0.01). In addition, limbal cDCs displayed significantly increased migratory kinetics in DED, including mean track speed, 3D instantaneous velocity, track length, and displacement, compared to naïve mice (all p < 0.05). In mice with DED, cDCs showed a higher meandering index in the limbus compared to central cornea ( p < 0.05). In DED, cDCs were less frequently found in contact with nerves in the limbus, peripheral, and central cornea ( p < 0.05). cDCs in contact with nerves demonstrated a larger surface area ( p < 0.001) and volume ( p < 0.001), however, they exhibited less sphericity ( p < 0.05) as compared to cDCs not in contact with nerves in naïve mice. Importantly, cDCs in contact with nerves during DED had a decreased track length, displacement, mean track speed, and 3D instantaneous velocity compared to those not in contact with nerves (all p < 0.05). Taken together, we present in vivo evidence of altered cDC kinetics and 3D morphology in DED. Furthermore, apparent neuronal contact significantly alters cDC kinetics and morphological characteristics, suggesting that ocular surface nerves may play a direct role in mediating immune responses in DED.<br /> (Copyright © 2020 Jamali, Seyed-Razavi, Chao, Ortiz, Kenyon, Blanco, Harris and Hamrah.)
- Subjects :
- Animals
Cell Movement immunology
Disease Models, Animal
Female
Kinetics
Limbus Corneae innervation
Mice
Mice, Inbred C57BL
Mice, Transgenic
Optic Nerve immunology
Dendritic Cells immunology
Dry Eye Syndromes diagnostic imaging
Dry Eye Syndromes immunology
Intravital Microscopy methods
Limbus Corneae diagnostic imaging
Limbus Corneae immunology
Microscopy, Fluorescence, Multiphoton methods
Subjects
Details
- Language :
- English
- ISSN :
- 1664-3224
- Volume :
- 11
- Database :
- MEDLINE
- Journal :
- Frontiers in immunology
- Publication Type :
- Academic Journal
- Accession number :
- 32457740
- Full Text :
- https://doi.org/10.3389/fimmu.2020.00742