April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
Up-Regulation of Micro-RNA-125b (chr 11q24; chr 21q21) in Retinoic Acid-Induced, and in Aging, Retinal Pigment Epithelial (ARPE-19) Cells
Author Affiliations & Notes
  • W. J. Lukiw
    Neuroscience & Ophthalmology, Lousiana State Univers Health Sci Center, New Orleans, Louisiana
  • P. K. Mukherjee
    Neuroscience & Ophthalmology, Lousiana State Univers Health Sci Center, New Orleans, Louisiana
  • J.-G. Cui
    Neuroscience & Ophthalmology, Lousiana State Univers Health Sci Center, New Orleans, Louisiana
  • N. G. Bazan
    Neuroscience & Ophthalmology, Lousiana State Univers Health Sci Center, New Orleans, Louisiana
  • Footnotes
    Commercial Relationships  W.J. Lukiw, None; P.K. Mukherjee, None; J.-G. Cui, None; N.G. Bazan, None.
  • Footnotes
    Support  in part by the Alzheimer’s Association, NIH EY05121, CNIB, Southern Eye Bank
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 4095. doi:
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      W. J. Lukiw, P. K. Mukherjee, J.-G. Cui, N. G. Bazan; Up-Regulation of Micro-RNA-125b (chr 11q24; chr 21q21) in Retinoic Acid-Induced, and in Aging, Retinal Pigment Epithelial (ARPE-19) Cells. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4095.

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

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Abstract

Purpose: : Micro RNAs (miRNAs) are potent post-transcriptional modulators of gene expression that regulate the stability and translation of their target messenger RNA (mRNA). This study examined miRNA complexity in all-trans-retinoic-acid (RA) induced, aging ARPE-19 cells, and in RA-stressed neuronal-glial co-cultures of human neural (HN) cells.

Methods: : ARPE-19 cell culture; bioinformatics (Silicon Genetics, Redwood City, CA); DNA array (Affymetrix, Santa Clara, CA); Northern analysis; primary HN cell culture; retinoic acid; RT-PCR; statistical analysis; Western analysis.

Results: : A human brain cell-enriched miRNA-125b, known to be associated with cellular proliferation, neural-derived cellular differentiation, brain cell fate and survival was significantly up-regulated in all-trans RA-stressed ARPE-19 and HN cells. The up-regulation of miRNA-125b was associated with the rate of growth of ARPE-19 and HN cells, and also linked to a reduction in the expression, at both the mRNA and protein level, of the cyclin-dependent kinase inhibitor 2A (CDKN2A), a known miRNA-125b target and negative regulator of cellular proliferation.

Conclusions: : miRNAs are powerful effectors of retinal and neural genetic signaling. A brain-enriched miRNA-125b appears to be involved in growth of ARPE-19 and primary HN cell neuronal-glial co-cultures, in part through the down-regulation of the cell cycle regulator CDKN2A. Other specific mRNA targets for miRNA-125b are currently under investigation. Pharmacotherapeutic strategies targeted at altering miRNA-125b abundance and neutralizing this small RNA’s pathogenic effects may be useful in the clinical treatment of both retinal and neurodegenerative disease.

Keywords: gene microarray • aging • gene/expression 
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