July 2018
Volume 59, Issue 9
Free
ARVO Annual Meeting Abstract  |   July 2018
Role of macrophage microRNA-150 in age-related macular degeneration
Author Affiliations & Notes
  • Jonathan Lin
    Ophthalmology & Visual Sciences, Washington University School of Medicine, Saint Louis, Missouri, United States
  • Harsh V Moolani
    Ophthalmology & Visual Sciences, Washington University School of Medicine, Saint Louis, Missouri, United States
  • Abdoulaye Sene
    Ophthalmology & Visual Sciences, Washington University School of Medicine, Saint Louis, Missouri, United States
  • Rohini Sidhu
    Medicine, Washington University School of Medicine, Saint Louis, Missouri, United States
  • Joseph B Lin
    Ophthalmology & Visual Sciences, Washington University School of Medicine, Saint Louis, Missouri, United States
  • Zhenyu Dong
    Ophthalmology & Visual Sciences, Washington University School of Medicine, Saint Louis, Missouri, United States
  • Norimitsu Ban
    Ophthalmology & Visual Sciences, Washington University School of Medicine, Saint Louis, Missouri, United States
  • Daniel S Ory
    Medicine, Washington University School of Medicine, Saint Louis, Missouri, United States
  • Rajendra Apte
    Ophthalmology & Visual Sciences, Washington University School of Medicine, Saint Louis, Missouri, United States
    Medicine, Washington University School of Medicine, Saint Louis, Missouri, United States
  • Footnotes
    Commercial Relationships   Jonathan Lin, None; Harsh Moolani, None; Abdoulaye Sene, None; Rohini Sidhu, None; Joseph Lin, None; Zhenyu Dong, None; Norimitsu Ban, None; Daniel Ory, None; Rajendra Apte, None
  • Footnotes
    Support  NIH Grants R01 EY019287, P30 EY02687, P30 DK020579, UL1 TR000448, P30 CA91842, T32 GM07200, UL1 TR002345, TL1 TR002344; the Starr Foundation; the Carl Marshall Reeves and Mildred Almen Reeves Foundation; the Bill and Emily Kuzma Family Gift for retinal research; Research to Prevent Blindness; the Jeffrey Fort Innovation Fund; the Thome Foundation
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 5558. doi:https://doi.org/
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    • Get Citation

      Jonathan Lin, Harsh V Moolani, Abdoulaye Sene, Rohini Sidhu, Joseph B Lin, Zhenyu Dong, Norimitsu Ban, Daniel S Ory, Rajendra Apte; Role of macrophage microRNA-150 in age-related macular degeneration. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5558. doi: https://doi.org/.

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

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Abstract

Purpose : Age-related macular degeneration (AMD) is a leading cause of blindness in adults over 50 years of age in industrialized countries. We and others have reported that aged macrophages exhibit functional changes in their activation status and in their ability to maintain cholesterol homeostasis and thereby promote AMD. However, the role of microRNAs (miRs) in regulating these AMD-promoting functional shifts in aged macrophages is underexplored. The goal of this study was to identify the miRs that coordinate the transcriptomic changes in macrophages that promote AMD pathogenesis and cause blindness.

Methods : To identify miRs that promote the transition of macrophages to the AMD-promoting phenotype, we performed a miR microarray, comparing macrophages from 6-8-week-old mice and 18-month-old wild-type mice. We then examined the cellular phenotype associated with miR-150 overexpression by RNA-Sequencing followed by pathway analysis for enriched gene ontology (GO) processes, process networks, and pathway maps with MetaCore. To validate the translational relevance of our findings, we quantified miR-150 levels in the peripheral blood mononuclear cells (PBMCs) of human AMD patients (N = 43) and control subjects without AMD (N = 63). For all analysis, we considered P < 0.05 to be statistically significant.

Results : MiR-150 had the highest fold changes in aged macrophages with ~9-fold higher expression in old peritoneal macrophages (P < 0.0001), ~3-fold higher expression in old splenic macrophages (P < 0.01), and ~3-fold higher expression in old bone marrow-derived macrophages (P < 0.05). Macrophages overexpressing miR-150 exhibited an altered transcriptomic profile enriched for the pathway map of aberrant lipid trafficking and metabolism in AMD pathogenesis (P=4.4×10-5; FDR=5.5×10-3). AMD patients had significantly higher PBMC miR-150 levels compared to control subjects (P < 0.0001). A gender- and age-adjusted binary logistic regression model confirmed that a ten-fold increase in PBMC miR-150 levels was associated with a 29.0-fold increased odds of having AMD (95% CI: 5.9-141.5).

Conclusions : Our results demonstrate that miR-150 is upregulated in AMD-promoting macrophages and implicate miR-150 as pathogenic in AMD. Ultimately, our results identify not only potential therapeutic targets for modulating the transition to the aged macrophage phenotype but also a potential biomarker for monitoring AMD progression.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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