June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
Upregulation of miR-146a in retina in rodent models of elevated intraocular pressure
Author Affiliations & Notes
  • Guorong Li
    Ophthalmology, Duke Eye Center, Durham, NC
  • Mohammadali Almasieh
    Pathology and Cell Biology, Université de Montréal, Montreal, QC, Canada
  • Coralia Luna
    Ophthalmology, Duke Eye Center, Durham, NC
  • Jianming Qiu
    Ophthalmology, Duke Eye Center, Durham, NC
  • Pratap Challa
    Ophthalmology, Duke Eye Center, Durham, NC
  • Molly Walsh
    Ophthalmology, Duke Eye Center, Durham, NC
  • Henry Tseng
    Ophthalmology, Duke Eye Center, Durham, NC
  • David Epstein
    Ophthalmology, Duke Eye Center, Durham, NC
  • Adriana Di Polo
    Pathology and Cell Biology, Université de Montréal, Montreal, QC, Canada
  • Pedro Gonzalez
    Ophthalmology, Duke Eye Center, Durham, NC
  • Footnotes
    Commercial Relationships Guorong Li, None; Mohammadali Almasieh, None; Coralia Luna, None; Jianming Qiu, None; Pratap Challa, None; Molly Walsh, None; Henry Tseng, None; David Epstein, None; Adriana Di Polo, None; Pedro Gonzalez, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 770. doi:https://doi.org/
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      Guorong Li, Mohammadali Almasieh, Coralia Luna, Jianming Qiu, Pratap Challa, Molly Walsh, Henry Tseng, David Epstein, Adriana Di Polo, Pedro Gonzalez; Upregulation of miR-146a in retina in rodent models of elevated intraocular pressure. Invest. Ophthalmol. Vis. Sci. 2013;54(15):770. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: Glaucoma caused by elevated intraocular pressure (IOP) can lead to retinal ganglion cell (RGC) pathology and a progressive vision loss. RGC degeneration in glaucoma is accompanied by a neuroinflammatory response, but the molecular mechanism that regulates this process is poorly understood. Since miR-146a is a negative regulator of cytokine expression, we hypothesized that miR-146a may be involved in regulating the retinal inflammatory response observed in glaucoma.

Methods: Expression of miR-146a in rodent retina was evaluated by qPCR and in situ hybridization. Elevated IOP was generated in rats by either laser trabecular photocoagulation or episcleral vein injection of hypertonic saline, and in mice by conditional knockout of DICER1 in the cells of the outflow pathway. To evaluate a possible negative feedback effect between inflammatory mediators and miR-146a, mixed rat retina cell cultures were treated with TNFα, and expression of miR-146a was analyzed by qPCR. Additionally, transient overexpression of a miR-146a mimic or scrambled control using NeuroMag transfection was followed by qPCR analysis of inflammatory markers (IL1α, IL1β, IL6, and TNFα). Finally, the effect of complete deletion of miR-146a was examined in retinas of 7 week old miR-146a knockout mice.

Results: Baseline miR-146a expression in rat retinas was observed by both in situ hybridization and PCR. In response to elevated IOP, miR-146a upregulation was detected in several animal models (i. laser trabecular photocoagulation in rats: 1wk: 1.5±0.13 folds, p=0.1266, n=3; 3wks: 2.08±0.24 folds, p=0.00495, n=3; ii. episcleral vein injection of hypertonic saline: 1wk: 1.99±0.65 folds, p=0.021, n=4; 3wks: 2.67±1.48, p=0.021, n=4; iii. Dicer KO in mice: 1.68±0.57 folds, p=0.0012, n=11 compared to the contralateral non-treated control retinas). Treatment of cultured retinal cells with TNFα for 30h led to a dose responsive increase in miR-146a expression. Conversely, transient overexpression and knockout of miR-146a led to a significant decrease and increase, respectively, of IL1α, IL1β, IL6, and TNFα.

Conclusions: Our results suggest that miR-146a forms a negative feedback loop that reduces the levels of expression of inflammatory mediators in the retina. Pressure-induced up-regulation of miR-146a in the retina could play a protective role by limiting potentially deleterious effects of inflammatory mediators in high-pressure glaucoma.

Keywords: 694 retinal culture • 568 intraocular pressure • 557 inflammation  
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