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Ying Li, Ru Jun Jin, Lan Li, HYEON JEONG YOON, In-Cheon You, Kyung Chul Yoon; Expression and Role of Nucleotide-binding Oligomerization Domain 2 (NOD2) in the Ocular Surface of Murine Dry Eye. Invest. Ophthalmol. Vis. Sci. 2019;60(9):268. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate expression and role of nucleotide-binding oligomerization domain 2 (NOD2) in the ocular surface of dry eye, which is a NOD-like receptor member and is involved in innate immune response.
C57/BL6 female mice were divided into untreated (UT), experimental dry eye (EDE) and NOD2 knockout (KO) groups, and EDE and NOD2 KO groups created by desiccating stress for 14 days. Tear volume, tear film break-up time (TBUT), and corneal staining scores were measured at 7 and 14 days after induction. Expression of NOD2 in the ocular surface was evaluated using immunofluorescence at 14 days. Western blot for RIP2 and NF-kB were performed in the cornea and conjunctiva at 14 days. Concentrations of IL-1β, IL-6, IFN-γ, and TNF-α were measured in the cornea and conjunctiva using a multiplex immunobead assay at 14 days. Flow cytometric analysis for CD11b, DCF-DA, and CD4+CCR5+ T cells was also performed. Goblet cell density and apoptosis positive cells were observed using PAS staining and TUNEL staining.
After desiccating stress, NOD2 was expressed in the cornea and conjunctiva of the EDE group. The NOD2 KO group showed a significant improvement in tear volume, TBUT, and corneal staining scores compared to the EDE group. Decreased expression of RIP2 and NF-kB was noted in the NOD2 KO group. Concentrations of IL-1β, IL-6, IFN-γ, and TNF-α and numbers of CD11b+ and CD4+CCR5+ T cells were lower in the NOD2 KO group than in the EDE group. Decreased DCF-DA and apoptosis positive cells and increased goblet cell density were observed in the NOD2 KO group compared to the EDE group (all p<0.05). In all results, EDE and NOD2 KO groups showed significant differences compared to the group.
The NOD2 receptor pathway induced inflammation and apoptosis by activation of RIP2 and NF-kB on the ocular surface after dry eye induction, thereby reducing tear secretion. Therefore, the NOD pathway may be involved in the pathogenesis of dry eye.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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