Expression of Nod-like Receptors and Clinical Correlations in Patients With Dry Eye Disease

Abstract

To investigate the expression pattern of nucleotide-binding oligomerization domain (Nod)-like receptors that detects "danger" intracellular signaling and its correlation with clinical dry eye (DE) markers. Cross-sectional study. A total of 50 participants with 50 eyes were included: 23 eyes with Sjögren syndrome (SS)-DE, 14 eyes with non-SS-DE, and 13 healthy controls with non-DE. Ocular Surface Disease Index (OSDI) was self-answered and clinical tests including the tear film breakup time (TBUT), Schirmer test, and corneal fluorescein staining (CFS) were performed. Specimens for expression pattern analysis were obtained by conjunctival impression cytology and biopsy. Nod-1, inhibitor kappa B kinase-alpha (IκKα), and nuclear factor kappa B (NF-κB) expression was determined by reverse transcription quantitative real-time polymerase chain reaction and Western blot. Correlations between Nod-1 and ocular surface parameters were determined. Patients with SS-DE had significantly higher OSDI and CFS scores and lower TBUT and Schirmer test scores than those with non-SS-DE patients (all P < .05). Compared with the control group, both the SS-DE and non-SS-DE groups showed significant upregulation in mRNA expression levels of Nod-1 (relative 3.48-fold and 1.72-fold upregulation, respectively, P < .01), IκKα (relative 1.83-fold and 1.24-fold upregulation, respectively, P < .01), and NF-κB (relative 1.84-fold and 1.32-fold upregulation, respectively, P < .01). Western blot analysis showed that Nod-1 protein expression increased in both the SS-DE and non-SS-DE groups (relative 2.71-fold and 1.64-fold upregulation, respectively, P < .05) compared with that in the control group. Similar findings were observed for IκKα and NF-κB. In DE participants, the expression of Nod-1 significantly correlated with the OSDI (R2= 0.61, r= 0.78, P<.01), Schirmer test score (R2= 0.44, r= -0.66, P < .01), and CFS (R2= 0.46, r= 0.68, P < .01) but did not significantly correlate with TBUT (R2 <0.01, r= 0.08, P= .66). Nod-1 expression was increased in the conjunctiva of DE, especially SS-DE, and was associated with disease severity. Expression of Nod-like receptors might play an important role in initiating the inflammatory response in DE.