September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
miR15a/16 mediates protective effects of beta-adrenergic signaling to reduce leukostasis in diabetic retinopathy
Author Affiliations & Notes
  • Li Liu
    Anatomy and Cell Biology, Wayne State University, Detroit, Michigan, United States
  • Eun-Ah Ye
    Anatomy and Cell Biology, Wayne State University, Detroit, Michigan, United States
  • Jena J Steinle
    Anatomy and Cell Biology, Wayne State University, Detroit, Michigan, United States
  • Footnotes
    Commercial Relationships   Li Liu, None; Eun-Ah Ye, None; Jena Steinle, None
  • Footnotes
    Support  NIH EYR01022045, RPB, NIH P30EY004068
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 3211. doi:
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    • Get Citation

      Li Liu, Eun-Ah Ye, Jena J Steinle; miR15a/16 mediates protective effects of beta-adrenergic signaling to reduce leukostasis in diabetic retinopathy. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3211.

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

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Abstract

Purpose : The cellular mechanisms of diabetes-induced retinal dysfunction still not clear. Our previous studies show that beta-adrenergic receptor agonist treatment is effective in reducing VEGF and protects the rodent retina from neuronal, vascular and functional damage in response to hyperglycemia. In this study, we investigated whether miR15a/16 plays a role in reducing leukostasis, and whether this response is mediated through IGFBP-3 regulation of TNFa and IL-1b.

Methods : miR15a/16 floxed mice (B6-129S-mirc30.tm1.1rdf) and B6.FVB-Tg (cdh5-cre)7Mlia/J Cre mice purchased from Jackson labs were cross bred to produce endothelial cell specific miR15a/16 conditional knockout mice. At 3 months of age, miR15a/16 floxed and miR15a/16 Cre-Lox mice were used. Some mice were sacrificed for leukostasis analyses (immunohistochemistry staining for Isolectin IB4-labeled blood vessels and CD45 labeled-leukocytes). Additional mice were used for Western blotting and ELISA analyses of TNFa, IL-1b, and IGFBP-3. For Western blotting, data will be compared to beta actin and optical density measurements will be provided (O.D.)

Results : Confocal microscopy showed more CD45 labeled leukocytes in miR15a/16 Cre-Lox mice compared to miR15a/16 floxed only mice. Also miR15a/16 floxed mice have decreased TNFa and IL-1b levels, with increased IGFBP-3 as compared to the miR15a/16 Cre-Lox mice.

Conclusions : The data demonstrate that miR15a/16 is key to regulating retinal leukostasis and inflammation, as well as the cellular signaling pathways that mediate these responses. IGFBP-3 may be at the heart of these findings, suggesting that therapeutics designed to increase IGFBP-3 levels will offer potential for drug development, with miR15a/16 as potential starting points.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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