Abstract
Ocular surface mucins are thought to play vital roles in maintaining the homeostasis of the pre-ocular surface tear film. We performed ocular surface tests with impression cytology to assess the expression levels of mucin-related genes on the ocular surface in healthy eyes. In addition, we investigated alterations in mucin-related gene expression secondary to treatment with rebamipide ophthalmic suspension in patients with Sjögren's syndrome-associated dry eyes (SS-DE). Thirty-three healthy individuals (control group) and 13 patients from our hospital with SS-DE were enrolled. Impression cytology was performed using Schirmer's test paper for RNA sampling. The mRNA levels of SAM-pointed domain-containing ETS-like factor (SPDEF), mucin 5AC (MUC5AC), and mucin 16 (MUC16) were determined using a real-time reverse transcription-polymerase chain reaction. The ocular surface test was performed once for the control group, and at baseline as well as 2, 4, 8, and 12 weeks after treatment in the Sjögren's syndrome-associated dry eyes group. mRNA levels of SPDEF, MUC5AC, and MUC16 were not significantly different between the control and SS-DE groups before rebamipide ophthalmic suspension treatment. SPDEF mRNA levels in control subjects were significantly correlated with levels of MUC5AC. Among SS-DE patients, SPDEF mRNA levels were significantly increased at 2, 4, and 8 weeks after treatment compared with baseline levels. MUC16 mRNA levels were significantly decreased from baseline levels at 4 and 8 weeks post-treatment. Ocular surface test using impression cytology is a clinically useful tool for assessing mucous conditions on the ocular surface and can be used to determine the effects of instillation treatment with eye drops that affect mucin production at the ocular surface.
Highlights
We investigated the relationship between the age of the participants and expression levels of mucin-related genes on the ocular surface using the partial correlation method
Among the mucin-related genes, a significant correlation was found between mucin 5AC (MUC5AC) and SAM-pointed domain-containing ETS-like factor (SPDEF) mRNA expression levels (Fig 2 and Table 2)
When SPDEF, MUC5AC, and mucin 16 (MUC16) mRNA expression levels on the ocular surface of patients were examined, we found that SPDEF mRNA expression levels at 2, 4, and 8 weeks after the initiation of rebamipide treatment had increased significantly (p = 0.0350, 0.0012, and 0.0069 at 2, 4, and 8 weeks, respectively, mixed-effects models; Fig 4A), but not at 12 weeks
Summary
The primary objective of this study was to clarify the normal range of mucin-associated gene expression levels in the ocular surface of healthy volunteers using a cross-sectional analysis
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