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Qinghai Peng, Wenhu Huang, Walter Collette, Michelle Twamley, Shirley Aguirre, Annette John-Baptiste; Circulating miRNAs as Biomarkers of Retinal Toxicity. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1947.
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To examine whether circulating retinal-enriched microRNAs were altered post treatment in a drug induced retinal toxicity study in rat.
Wistar Hans rats were administered a single intravitreal injection of either a pan-CDK inhibitor (10 or 30 µg/eye) or a HSP90 inhibitor (9 or 27 µg/eye). EDTA whole blood samples were collected predose, and on days 1, 3 and 7 post dose. Retinal-enriched miRNAs and the liver-enriched miR-192 (used as a control) were analyzed by qRT-PCR. Electroretinography (ERG) was performed predose and at end of study to assess retinal function. Eyes were collected either on day 8 or at 2 weeks post dose and processed for histopathologic evaluation.
Elevations of plasma miR-124a, miR-96, and miR-183 peaked on day 3 post dose in the pan-CDKi high dosed animals demonstrating greater than 300X, 10X and 6X fold increases respectively in a time-dependent manner . The low dose group of the pan-CDKi treated animals demonstrated slight elevations of miR-124a, miR-96 and miR-183. Neither dose group in the pan-CDKi treated animals demonstrated any change in miR-192 and retinal degeneration was confirmed by ERG and histopathology. Comparatively, the HSP90 treated group, exhibited no changes in miRNA levels, ERG or histopathology.
This study demonstrated plasma miR-96, miR-124a, and miR-183 are strong contenders as retinal toxicity biomarkers. Although these miRNAs need additional validation whether they truly predict retinal toxicity or not prior to histopathology, these results provide promise for further test using additional retinal toxicants.
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