Some of the differently expressed miRNAs we found have already been reported in other studies as indicative of retinal damage. For instance, the differently expressed miRNAs in our study, miR-200a-3p and miR-200b-3p (S-POAG vs. M-POAG, POAG vs. cataract), were found to be critical regulators of POAG induced by the mutation of the OPTN (E50K) gene, which participates in neurodegeneration by induction of apoptosis of retinal ganglion cells in transgenic mice models and progressive retinal degeneration exclusively in the peripheral region of the retinas.
46 Drewry et al.
47 also found that miR-200a-3p, miR-200b-3p, miR-200c-3p, miR-141-3p, and miR-429 were differently expressed in normal human ciliary body, cornea, and trabecular meshwork through next-generation sequencing. These five miRNAs were all validated to target the ZFPM2 gene, also known as FOG2, which was glaucoma related.
48 ZFPM2 was observed to be upregulated after injury to the optic nerve
49 and may have a role in ocular development.
50 The differently expressed miRNA in our study, miR-16 (S-POAG vs. M-POAG, POAG vs. cataract), was significantly dysregulated in the glaucomatous retina of rat eyes with advanced nerve damage induced by elevated IOP.
51 Moreover, hsa-miR-183-5p and hsa-miR-96-5p were significantly differently expressed between POAG and cataract eyes in our study. Stephen et al.
52 found that the knockout of miR-183/96/182 cluster in mice results in early-onset and progressive synaptic defects of the photoreceptors, leading to abnormalities of scotopic and photopic electroretinograms, with decreased b-wave amplitude as the primary defect and progressive retinal degeneration. In addition, inactivation of the miR-183/96/182 cluster resulted in global changes in retinal gene expression, and these changes play an important role in postnatal functional differentiation and synaptic connectivity of photoreceptors. All these studies concerning specific miRNA functions in vivo support our results of differential miRNA profiles in POAG eyes. However, some of the differently expressed miRNAs between the POAG and cataract groups may be related to cataract development rather than POAG. For example, hsa-miR-125b-5p, which was differently expressed when comparing the POAG group with the cataract group in our study, was reported to inhibit lens epithelial cell apoptosis by targeting gene p53 in age-related cataracts.
53