July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
NF-kB-upregulated microRNA (miRNA) in age-related macular degeneration (AMD) and Alzheimer's disease (AD) contribute interactively to altered innate-immunity, amyloidogenesis and inflammatory neurodegeneration
Author Affiliations & Notes
  • Walter J Lukiw
    Neurology, Neuroscience & Ophthalmology, Lousiana State Univ Hlth Sci Ctr, New Orleans, Louisiana, United States
    Toronto, Alchem Biotek, Toronto, Ontario, Canada
  • Yuhai Zhao
    Neurology, Neuroscience & Ophthalmology, Lousiana State Univ Hlth Sci Ctr, New Orleans, Louisiana, United States
  • Vivian Jaber
    Neurology, Neuroscience & Ophthalmology, Lousiana State Univ Hlth Sci Ctr, New Orleans, Louisiana, United States
  • Footnotes
    Commercial Relationships   Walter Lukiw, None; Yuhai Zhao, None; Vivian Jaber, None
  • Footnotes
    Support  COBRE III Pilot Project NIH/NIGMS Grant P30-GM103340, an unrestricted grant to the LSU Eye Center from Research to Prevent Blindness (RPB); the Louisiana Biotechnology Research Network (LBRN) and NIH grants NEI EY006311, NIA AG18031 and NIA AG038834
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 3016. doi:
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    • Get Citation

      Walter J Lukiw, Yuhai Zhao, Vivian Jaber; NF-kB-upregulated microRNA (miRNA) in age-related macular degeneration (AMD) and Alzheimer's disease (AD) contribute interactively to altered innate-immunity, amyloidogenesis and inflammatory neurodegeneration. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3016.

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

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Abstract

Purpose : Age-related macular degeneration (AMD) of the retina and Alzheimer's disease (AD) of the brain represent two complex neurodegenerative disorders: (i) that involve the progressive dysregulation of multiple-neurobiological signaling pathways; (ii) that exhibit the temporal accumulation of pro-inflammatory lesions including the drusen of AMD and the Aβ-peptide-containing senile plaques of AD; and (iii) that culminate in an insidious neurodegeneration ending in neural-cell atrophy and death, and progressive-loss of cognition and central visual-function. Using high-integrity total-RNA samples from AMD-retina or AD-brain, RNA sequencing and a micro-fluidic-array approach, the purpose of these studies was threefold: (i) to quantify microRNA (miRNA) speciation and complexity common to both AD and AMD; (ii) to analyze their links to down-regulated messenger RNA (mRNA) families affected; and (iii) to analyze these effects on multiple neurobiological signaling pathways in AMD retina and AD brain.
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Methods : Bioinformatics algorithms, cultured microglial, neuronal and RPE cells; human AMD, AD and control tissues; immunohistochemistry, micro-fluidic-hybridization, mRNA-miRNA arrays; NF-kB inhibitors, LED-Northern dot blot, RNA sequencing, stabilized anti-miRNA, transgenic murine models for AD and AMD (TgAMD); Western analysis.

Results : Here for the first time we report the RNA sequence of an octet of miRNAs including miRNA-7, miRNA-9-1, miRNA-23a/miRNA-27a, miRNA-34a, miRNA-125b-1, miRNA-146a and miRNA-155 that are significantly-increased in abundance and common to both AMD and AD. Bioinformatics, miRNA-mRNA complementarity, next-generation RNA sequencing and feature-alignment-analysis further indicate that these miRNAs have potential to interact with, and down-regulate, ~9460 target-mRNAs (about 3.5% of the genome) involved in the synchronization of amyloid-production and clearance, phagocytosis, innate-immune, pro-inflammatory and neurotrophic signaling and/or synaptogenesis in diseased tissues.

Conclusions : Multiple pathogenetic pathways involving miRNA and mRNA are common to both AMD and AD. These involve analogous pathological signaling-defects and disease-mechanisms at the molecular-genetic level which drive inflammatory-neuropathology and retinal- and neural-cell decline.

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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