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Takashi Kojima, Taeko Nagata, Shigeru Nakamura, Murat Dogru, Kazuo Tsubota; Tear function and ocular surface abnormalities under environmental stress conditions in the Nrf2(-/-) Mouse. Invest. Ophthalmol. Vis. Sci. 2014;55(13):3655.
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A healthy ocular surface is essential to maintain stable visual function and ocular barrier functions. Nuclear factor erythroid2-related factor-2 (Nrf2) is a transcription factor that regulates downstream target genes encoding biological defense enzymes including antioxidant and detoxification enzymes to protect the tissues. We used the Nrf2(-/-) mice and investigated the effect of environmental stress conditions on the ocular surface and tear functions.
Thirty week old C57/B6 wild type mice (wt) and Nrf2 (-/-) mice (6 mice in each group) were used for evaluations of the tear volume, tear film stability (tear film break-up time), vital staining including fluorescein and Rose Begal staining before and after exposure to environmental stress. Mice were kept in a small compartment and exposed to continuous air flow for 4 hours (environmental stress mouse model).
After exposure to stress conditions, tear secretion significantly decreased in both wild type (p= 0.0015) and Nrf2 (-/-) mice (p=0.0043). Mean percentage of tear secretion reduction in Nrf2 (-/-) mice (32.8±16.6%) was significantly higher than the wild type mice (17.2±13.8%) (p= 0.017). Tear film break-up time after stress in the Nrf2 (-/-) mice was significantly shorter than the wild type mice after exposure to the stress conditions (p=0.036). There were no differences in the mean fluorescein staining scores after stress exposure between the Nrf2 (-/-) mice (3.5±1.3 points) and the wild type mice (2.8±1.7 points) (p=0.158). The mean Rose Bengal score after stress exposure in the Nrf2 (-/-) mice (3.4±0.9 points) was significantly higher than the wild type mice (2.3±0.8 points) (p=0.01).
The current study revealed that Nrf2 is involved in the pathogenesis of ocular surface damage and decreased tear secretion under environmental stress conditions.
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