TY - JOUR
T1 - The effect of Nrf2 knockout on ocular surface protection from acute tobacco smoke exposure
T2 - Evidence from Nrf2 knockout mice
AU - Kojima, Takashi
AU - Dogru, Murat
AU - Higuchi, Akihiro
AU - Nagata, Taeko
AU - Ibrahim, Osama M.A.
AU - Inaba, Takaaki
AU - Tsubota, Kazuo
N1 - Funding Information:
Supported by research grant FP01210115 from the Smoking Research Foundation .
Publisher Copyright:
© 2015 American Society for Investigative Pathology.
PY - 2015/3/1
Y1 - 2015/3/1
N2 - Ocular surface mucosa is the first-line ocular tissue to be exposed to environmental stress. We evaluated tear functions and keratoconjunctival epithelial alterations after sidestream cigarette smoke (SCS) exposure and tried to clarify the role of the transcription factor nuclear factor erythroid 2-related factor 2 (Nfe2l2, also known as Nrf2), on the ocular surface. In wild-type and Nrf2-/- mice, tear volume did not change after SCS exposure. Tear film breakup time (tear stability) in Nrf2-/- mice was significantly shorter than that in wild-type mice after SCS exposure. Vital staining scores, including fluorescein and Rose Bengal staining, showed significantly higher values in Nrf2-/- mice than in wild-type mice after SCS exposure. Excessive oxidative stress accumulation was detected in Nrf2-/- mice after SCS exposure using immunohistochemical analysis. Immunohistochemical analysis also revealed decreased mucin 1 (Muc1) and Muc5ac staining in Nrf2-/- mice after SCS exposure. mRNA expression levels of Muc1, Muc4, and Muc5ac and of SAM-pointed domain epithelial-specific transcription factor in Nrf2-/- mice were lower than those in wild-type mice after SCS exposure. Mean tear IL-6 concentrations increased significantly in Nrf2-/- mice after SCS exposure. In conclusion, SCS exposure induced decreased tear stability, ocular surface damage, and altered conjunctival phenotype in Nrf2-/- mice. Nrf2 could play an important role in protection of the ocular surface against SCS exposure.
AB - Ocular surface mucosa is the first-line ocular tissue to be exposed to environmental stress. We evaluated tear functions and keratoconjunctival epithelial alterations after sidestream cigarette smoke (SCS) exposure and tried to clarify the role of the transcription factor nuclear factor erythroid 2-related factor 2 (Nfe2l2, also known as Nrf2), on the ocular surface. In wild-type and Nrf2-/- mice, tear volume did not change after SCS exposure. Tear film breakup time (tear stability) in Nrf2-/- mice was significantly shorter than that in wild-type mice after SCS exposure. Vital staining scores, including fluorescein and Rose Bengal staining, showed significantly higher values in Nrf2-/- mice than in wild-type mice after SCS exposure. Excessive oxidative stress accumulation was detected in Nrf2-/- mice after SCS exposure using immunohistochemical analysis. Immunohistochemical analysis also revealed decreased mucin 1 (Muc1) and Muc5ac staining in Nrf2-/- mice after SCS exposure. mRNA expression levels of Muc1, Muc4, and Muc5ac and of SAM-pointed domain epithelial-specific transcription factor in Nrf2-/- mice were lower than those in wild-type mice after SCS exposure. Mean tear IL-6 concentrations increased significantly in Nrf2-/- mice after SCS exposure. In conclusion, SCS exposure induced decreased tear stability, ocular surface damage, and altered conjunctival phenotype in Nrf2-/- mice. Nrf2 could play an important role in protection of the ocular surface against SCS exposure.
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U2 - 10.1016/j.ajpath.2014.11.014
DO - 10.1016/j.ajpath.2014.11.014
M3 - Article
C2 - 25701884
AN - SCOPUS:84925071349
SN - 0002-9440
VL - 185
SP - 776
EP - 785
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 3
ER -