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Shambhu D Varma, Krish Chandrasekaran; Micro RNA Upregulation in Diabetic lens. Invest. Ophthalmol. Vis. Sci. 2017;58(8):3180.
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© ARVO (1962-2015); The Authors (2016-present)
Oxidative stress is considered to be a major contributor to the pathogenesis of cataracts.. However, it is unknown how does oxidative stress deplete the endogenous antioxidant response pathway in the lens. We tested if this could be related to the upregulation of microRNAs and consequent silencing of transcription of antioxidant enzymes and NrF-2. The purpose of this investigation was thus to study the microRNA profile in diabetic lens.
Studies were done with lenses isolated from C57bl/6 mice rendered diabetic by streptozotocin (IV, 75mh/kg) for two consecutive days. Blood glucose varied 250-350 mg/dl. Eyes were enucleated after six weeks. The lenses from each mouse were pooled, frozen, RNA isolated and cDNAs were prepared. The miRs profile was then determined by Quantitative PCR array using QIAGEN miR finder (MIMM-001Z). The results were then expressed as fold ratios between the diabetic and normal lenses.
At least six miRs, namely miR-142p, miR-146a-5p, miR-200c-3p, miR374a-5p and miR-144-3p were significantly upregulated in the diabetic lenses, the fold ratios being 5.53, 2.16, 30, 21, 2.45, 3.78 and 9, 17 respectively. Upregulation values above 2 were considered significant. Functionally, based on sequence based information, upregulation of 200-c is expected to inhibit cellular differentiation, previously well noted histologically to be inhibited with cataract formation. The upregulation of miR-144 links with the down regulation of Nrf-2 involved in the transcription of antioxidant enzymes including thioredoxin reductase. The results thus correlate with our previous findings showing down regulation of this enzyme in the lenses exposed to oxidative stress and its normalization with sulforaphane. The significance of the changes in other miRs which are primarily immune-regulatory is not apparent in the lens.
The results demonstrate for the first time induction of these miRs in diabetic lenses. The specificity of their targets in terms of inhibition of the transcription of various antioxidant proteins in the diabetic lens and cataract formation are under progress.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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