Alterations of murine subbasal corneal nerves after environmental dry eye stress

Cem Simsek, Takashi Kojima, Murat Dogru, Kazuo Tsubota

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

PURPOSE. To investigate the morphologic changes in the corneal subbasal nerve (CSN) plexus in wild-type mice after exposure to environmental dry eye stress (EDES) using in vivo confocal microscopy (IVCM). METHODS. We examined 22 eyes of 8-week-old wild-type male mice (Balb/c, n = 11). The mice were exposed to an air fan inside a small compartment 5 hours/day for 3 days (EDES). Aqueous tear secretion and corneal epithelial damage were assessed. The CSNs were investigated by laser-scanning IVCM. Density; tortuosity; and reflectivity of CSNs; and dendritic cell (DC) densities were evaluated using semi-automated NeuronJ software. RESULTS. EDES significantly decreased the aqueous tear secretion quantity (P = 0.0019) and significantly increased the corneal fluorescein (P = 0.005) and lissamine green staining scores (P = 0003). The CSN density showed a significant decrease after EDES exposure (before, 2813 ± 762 pixels/frame; after, 1906 ± 896 pixels/frame, P = 0.0071). The tortuosity and the reflectivity grades did not show statistically significant differences after EDES exposure (tortuosity, P = 0.307; reflectivity, P = 0.758). However, the mean DC density showed a significant increase after EDES exposure (before, 12.62 ± 5.94 cells/mm2; after, 15.93 ± 5.30 cells/mm2, P = 0.026). CONCLUSIONS. Even short-term exposure to EDES induced alterations in the CSN plexus morphology including decreased subbasal corneal nerve density and increased amount of DCs in mice. The EDES mouse model is a promising model to study the ocular surface and corneal nerve changes associated with dry eye disease.

Original languageEnglish
Pages (from-to)1986-1995
Number of pages10
JournalInvestigative Ophthalmology and Visual Science
Volume59
Issue number5
DOIs
Publication statusPublished - 2018 Apr 1

Fingerprint

Environmental Exposure
Tears
Confocal Microscopy
Dendritic Cells
Cell Count
Eye Diseases
Fluorescein
Lasers
Software
Air
Staining and Labeling
Intravital Microscopy
Corneal Injuries

Keywords

  • Confocal microscopy
  • Corneal subbasal nerves
  • Dry eye
  • Environmental stress

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Alterations of murine subbasal corneal nerves after environmental dry eye stress. / Simsek, Cem; Kojima, Takashi; Dogru, Murat; Tsubota, Kazuo.

In: Investigative Ophthalmology and Visual Science, Vol. 59, No. 5, 01.04.2018, p. 1986-1995.

Research output: Contribution to journalArticle

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T1 - Alterations of murine subbasal corneal nerves after environmental dry eye stress

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N2 - PURPOSE. To investigate the morphologic changes in the corneal subbasal nerve (CSN) plexus in wild-type mice after exposure to environmental dry eye stress (EDES) using in vivo confocal microscopy (IVCM). METHODS. We examined 22 eyes of 8-week-old wild-type male mice (Balb/c, n = 11). The mice were exposed to an air fan inside a small compartment 5 hours/day for 3 days (EDES). Aqueous tear secretion and corneal epithelial damage were assessed. The CSNs were investigated by laser-scanning IVCM. Density; tortuosity; and reflectivity of CSNs; and dendritic cell (DC) densities were evaluated using semi-automated NeuronJ software. RESULTS. EDES significantly decreased the aqueous tear secretion quantity (P = 0.0019) and significantly increased the corneal fluorescein (P = 0.005) and lissamine green staining scores (P = 0003). The CSN density showed a significant decrease after EDES exposure (before, 2813 ± 762 pixels/frame; after, 1906 ± 896 pixels/frame, P = 0.0071). The tortuosity and the reflectivity grades did not show statistically significant differences after EDES exposure (tortuosity, P = 0.307; reflectivity, P = 0.758). However, the mean DC density showed a significant increase after EDES exposure (before, 12.62 ± 5.94 cells/mm2; after, 15.93 ± 5.30 cells/mm2, P = 0.026). CONCLUSIONS. Even short-term exposure to EDES induced alterations in the CSN plexus morphology including decreased subbasal corneal nerve density and increased amount of DCs in mice. The EDES mouse model is a promising model to study the ocular surface and corneal nerve changes associated with dry eye disease.

AB - PURPOSE. To investigate the morphologic changes in the corneal subbasal nerve (CSN) plexus in wild-type mice after exposure to environmental dry eye stress (EDES) using in vivo confocal microscopy (IVCM). METHODS. We examined 22 eyes of 8-week-old wild-type male mice (Balb/c, n = 11). The mice were exposed to an air fan inside a small compartment 5 hours/day for 3 days (EDES). Aqueous tear secretion and corneal epithelial damage were assessed. The CSNs were investigated by laser-scanning IVCM. Density; tortuosity; and reflectivity of CSNs; and dendritic cell (DC) densities were evaluated using semi-automated NeuronJ software. RESULTS. EDES significantly decreased the aqueous tear secretion quantity (P = 0.0019) and significantly increased the corneal fluorescein (P = 0.005) and lissamine green staining scores (P = 0003). The CSN density showed a significant decrease after EDES exposure (before, 2813 ± 762 pixels/frame; after, 1906 ± 896 pixels/frame, P = 0.0071). The tortuosity and the reflectivity grades did not show statistically significant differences after EDES exposure (tortuosity, P = 0.307; reflectivity, P = 0.758). However, the mean DC density showed a significant increase after EDES exposure (before, 12.62 ± 5.94 cells/mm2; after, 15.93 ± 5.30 cells/mm2, P = 0.026). CONCLUSIONS. Even short-term exposure to EDES induced alterations in the CSN plexus morphology including decreased subbasal corneal nerve density and increased amount of DCs in mice. The EDES mouse model is a promising model to study the ocular surface and corneal nerve changes associated with dry eye disease.

KW - Confocal microscopy

KW - Corneal subbasal nerves

KW - Dry eye

KW - Environmental stress

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