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Anita S. Chan, Sindhu Saraswathy, MinHee K. Ko, Narsing A. Rao; The Protective Role of MicroRNA-140 in Retinal Ischemia. Invest. Ophthalmol. Vis. Sci. 2011;52(14):517.
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© ARVO (1962-2015); The Authors (2016-present)
MicroRNAs (miRNAs) have been recently implicated as posttranscriptional gene regulators that are differentially expressed in critical biological and pathological cellular processes. Previously we demonstrated the protective effect of neuroglobin (Ngb) overexpression in transgenic mice (Ngb+/+) with retinal ischemia-reperfusion (IR) injury. By using high-throughput miRNA expression analysis, we investigated (a) the differential miRNAs expression in Ngb+/+ compared to wild type (WT) mice with IR retinal injury and (b) the protective effect of select miRNA mimic in IR injury of the retina by intravitreal delivery.
Retinal ischemia was induced in WT and Ngb+/+ transgenic mice by using the high intraocular pressure method. Animals were sacrificed at day 7 of reperfusion and the eyes were processed for miRNA pcr array (RT2 ProfilerTM miRNA PCR Array), histopathology and TUNEL assay for apoptosis. Retinal ischemia was also performed on WT mice in which miR-140 mimics (miRIDIAN Mimics, Dharmacon) were intravitreally injected at day 0 and day 3 of reperfusion. These animals were sacrificed at day 7 of reperfusion and the eyes processed for morphometric and immunohistochemical analysis for DNA damage and apoptosis.
The miRNA PCR array results revealed a robust upregulation of miR-140 in Ngb-IR mice compared to WT-IR mice, in association with neuroprotection in the retina on histopathology and TUNEL assay. Conversely, in WT-IR mice compared to non-ischemic WT control mice, miR-140 was profoundly down-regulated in association with retinal damage and apoptosis. Furthermore, neuroprotection in WT-IR mice with intravitreal miR-140 mimic injections was demonstrated on morphometric analysis revealing preservation of retinal thickness (p=0.02) and morphology, in addition to decreased DNA damage and apoptosis through decreased immunoreactivity for 8-hydroxydeoxyguanosine (a marker for DNA damage), caspase 3 and TUNEL positive cells.
The above novel results reveal (a) the protective effects of Ngb in IR retinal injury could be mediated by miR-140 and (b) the intravitreal delivery of this microRNA offers protection in preventing oxidative stress mediated retinal IR injury. However, the molecular mechanism for such beneficial effect is not clear.
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