Gene expression profile of Retinal Pigment Epithelium derived ARPE-19 cells under serum starvation

Tuesday, October 09, 2012 — Poster Session I
1:00 p.m. – 3:00 p.m	Natcher Conference Center, Building 45	NEI	AGING-5

Authors

• S. Mishra
• K.M. Peterson
• A.E. Berger
• G.J. Wistow

Abstract

Age Related Macular Degeneration (AMD), a major cause of vision loss, is associated with formation of subretinal deposits (drusen) and damage to Bruch’s membrane. Deprivation of serum factors may contribute to the stresses experienced by RPE cells in regions of such damage. We characterized changes to gene expression using microarray analysis on the human RPE-derived cell line ARPE19 over seven days of serum starvation. Two striking patterns were observed. Genes of cholesterol and fatty acid biosynthetic pathways were up-regulated during serum starvation. In addition, while many genes for zinc-binding proteins (including several Zn-fingers proteins)were upregulated, others involved in the regulation of intracellular zinc concentration, including metallothioneins, were suppressed. The results were confirmed by Q-PCR analysis. Supplementation with LDL during serum-starvation resulted in decreased expression of cholesterol and lipid metabolism genes. Supplementation with Zn resulted in increased expression of metallothionein genes. The results are interesting because both cholesterol and zinc have been implicated in AMD: cholesterol and zinc accumulate in subretinal deposits in AMD, and dietary zinc appears to be protective for AMD in population studies. This raises the possibility that serum-starvation of ARPE-19 cells may provide clues to some of the processes of disease progression in AMD.

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