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Hari Jayaram, William O Cepurna, Elaine C Johnson, John C Morrison; MicroRNA Expression Within The Glaucomatous Retina. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):1691.
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MicroRNAs (miRNAs) are small, endogenous non-coding RNAs that modulate post-transcriptional gene expression. Their role in the pathophysiology of ocular disease is a rapidly expanding field. Although the role of miRNAs upon the pathogenesis of glaucomatous damage is not known, there is supporting evidence from CNS research that highlight their potential importance. It was therefore hypothesized that miRNAs altered in CNS injury may also be altered in experimental glaucoma.
IOP was elevated in rats by unilateral injection of hypertonic saline and the IOP response monitored for 5 weeks. After sacrifice, retrobulbar optic nerve sections were graded for nerve damage. miRNA was extracted from the retinae of eyes with advanced nerve damage (n=8) and from normal fellow eyes as controls (n=8). Samples were reverse transcribed and pre-amplified for quantitative PCR using specific Taqman probes for a panel of twenty miRNAs. Results were normalized to U6sRNA and snoRNA234 with analysis of relative expression performed by the Livak method. Statistical comparison of miRNA expression between glaucoma and control retinae was performed by a two-tailed t-test with significance considered for values of p<0.05.
Induction of glaucomatous damage was confirmed in experimental eyes with a mean injury grade of 5.0 with mean/maximum IOPs of 39.2±3.2mmHg / 51.7±1.0mmHg compared to a mean injury grade of 1.0 with mean/maximum IOPs of 28.2 ±0.2 mmHg / 29.0±0.3mmHg in control eyes. Among the miRNAs hypothesized as likely to be affected, miR-16, let-7a, miR-181c, miR-497, miR-29b, miR-204, miR-106b and miR-25 were significantly downregulated in glaucomatous retinae compared to controls (p≤0.04) and a single miRNA, miR-27a, was significantly upregulated (p=0.01). No significant change in expression of miR-21, miR-22, miR23a, miR-145, miR-200b, miR-223 or miR-424 was observed.
This is the first study evaluating changes in microRNA expression between healthy and glaucomatous retinae. MicroRNAs altered within the retinae of eyes with advanced glaucomatous nerve damage are also known to be altered in CNS injury, with actions serving to modulate apoptosis, ischemic responses or TGF-β signaling. Further research to evaluate the role of microRNAs in the glaucomatous optic nerve head as well as retina to dissect the dynamic mechanisms of glaucomatous optic neuropathy, may ultimately lead to the identification of novel therapeutic targets.
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