miRNAs have been identified as promising diagnostic markers for various cardiovascular diseases,
7,39,40 cancer,
8 and neurological disorders.
41 In fact, more than 100 circulating miRNAs have been identified as biomarkers for different diseases.
42 Previous studies have also identified miRNAs in cell types relevant to ocular (patho)physiology,
14,16,43–45 vitreous humor,
46 and AqH.
47,48 Here, the combination of miR-637, miR-1306-5p, and miR-3159 displayed the strongest correlation with glaucoma/XFS. Neither miRNA had previously been described in an ocular context, nor associated with glaucoma or XFS. miR-637 was significantly elevated in both the AqH and plasma of patients compared to controls across both ethnic cohorts. miR-637 acts as a tumor suppressor in hepatocellular carcinoma
49 and gliomas,
50 and controls osteoblast and adipocyte differentiation,
51 and C-reactive protein expression.
52 In addition, miR-637 was identified as a putative predictive biomarker for long-term mortality after acute ischemic stroke.
52 Similar to miR-637, miR-608 was previously determined to have anti-oncogenic properties in hepatocellular carcinoma, possibly by modulating expression of macrophage inhibitory factor,
53 and in bladder cancer.
54 Of all the miRNAs studied in the custom array, miR-940 was the most abundant, in both sample types examined. In contrast to a previous report that miR-940 was differentially expressed in AqH of 10 glaucoma patients and 5 control subjects,
17 miR-940 expression levels did not differ between glaucoma and controls in our study. However, our results do coincide with the same prior study for miR-4725-3p: Both studies identified this miRNA as elevated in glaucoma (plasma and AqH in our study, AqH in Tanaka and colleagues
17). Circulating levels of miR-4448 were also consistently higher in glaucoma and XFS patients than cataract controls; a prior next-generation sequencing study identified miR-4448 as one of the more prevalent miRNAs in AqH.
38 Together, these studies validate our approach and suggest that the miRNAs identified here are putative biomarkers. Other miRNAs of interest described previously in glaucoma patients did not differ between patients and controls (including miR-143, miR-518d, miR-660, miR-3185, miR-3663-3p, and miR-4449) or were not tested on our array.
17,18,37