Conjunctival miRNAs as potential biomarkers in chronic ocular pain associated with dry eye disease: an explorative study

Abstract

Purpose: To analyze the presence of neuropathic and inflammatory pain microRNAs (miRNAs) in conjunctival epithelial cells of patients suffering from chronic ocular pain associated with dry eye disease (DED). Methods: Nineteen participants in this cross-sectional study were assigned to three groups (age- and sex- matched): 7 patients with chronic ocular pain associated with DED (pain-DED), 6 patients with DED but no pain (no pain-DED), and 6 subjects without DED or ocular pain (controls). Conjunctival epithelial cells were collected by impression cytology and the expression of 84 miRNAs related to neuropathic and inflammatory pain was analyzed by real time RT-PCR. miRNA expression was statistically compared among groups and correlated with symptomatology and clinical signs. Results: The expression of miR-154-5p, miR-181a-5p and miR-99a-5p was significantly downregulated in the pain-DED group compared to no pain-DED patients, whereas miR-223-3p was upregulated. MiR-124-3p, miR- 127-3p, miR-206, miR-302 d-3p, miR-376 b-5p, miR-543 and miR-665 were significantly upregulated in pain- DED patients compared to controls, while miR-99a-5p was downregulated. MiR-338-5p expression was upre- gulated in the no pain-DED group compared to controls. Furthermore, several significant correlations were found, the strongest being between NRS and miR-137 and miR-379-3p (r = 0.693), OSDI and miR-543 (r = 0.693), cold sensitivity and miR-339-5p (r = 0.685), and nerve length and miR-378a-3p (r = 0.665). Conclusions: Specific miRNA profiles may be related to the presence of DED and/or chronic ocular pain and represent promising candidate biomarkers. These findings contribute to a better understanding of the molecular mechanisms underlying chronic ocular pain associated with DED and might support the development of future therapeutic strategies.