Involvement of oxidative stress on corneal epithelial alterations in a blink-suppressed dry eye

Shigeru Nakamura, Michiko Shibuya, Hideo Nakashima, Ryuji Hisamura, Nozomi Masuda, Tomohiro Imagawa, Masato Uehara, Kazuo Tsubota

Research output: Contribution to journalArticlepeer-review

143 Citations (Scopus)


PURPOSE. To investigate whether oxidative stress is involved in the etiology of the corneal disorder in blink-suppressed dry eye in a clinically relevant in vivo rat model. METHODS. A series of treatments were performed under continuous exposure to low-humidity airflow. Rats were placed on a jogging board (JB) made of a plastic pipe for 7.5 h/d, and for 16.5 hours, they were placed in individual cages without a JB. This protocol was repeated for up to 30 days. Corneal surface alteration was evaluated by the score of punctate fluorescein staining. To assess oxidative stress status, the levels of damaged DNA, and the protein modification by reactive aldehydes in corneal epithelia were detected by immunohistochemistry, using 8-hydroxy-2-deoxyguanosine, 4-hydroxynonenal- and malondialdehyde-specific antibodies. RESULTS. Significant increases in the fluorescein staining score were observed from days 1 to 30 compared with the initial value. The average score for the dry eye group was significantly increased compared with that for the nontreatment group at all time points throughout the experiment. Immunoreactivity of all oxidative stress markers increased in the dry eye treatment. Quantitative analysis of the positive-stained cells showed a significant increase in the number of positive cells after 10 and 30 days in the dry eye treatment group compared with the nontreatment group. CONCLUSIONS. These results suggest a relationship between the accumulation of oxidative stress and the etiology of corneal epithelial alterations in blink-suppressed dry eye.

Original languageEnglish
Pages (from-to)1552-1558
Number of pages7
JournalInvestigative Ophthalmology and Visual Science
Issue number4
Publication statusPublished - 2007 Apr
Externally publishedYes

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience


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