Alterations of murine subbasal corneal nerves after environmental dry eye stress

Cem Simsek, Takashi Kojima, Murat Dogru, Kazuo Tsubota

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)


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
Issue number5
Publication statusPublished - 2018 Apr


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

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience


Dive into the research topics of 'Alterations of murine subbasal corneal nerves after environmental dry eye stress'. Together they form a unique fingerprint.

Cite this