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Neda Barzegar-Befroei, Jane Flinn, Gretchen Knaack, Christer Hogstrand, Arthur A. Bergen, Imre Lengyel; Gene Expression Changes In Aged Rat Eyes Following Oral Zinc Supplementation. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2320.
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Decreased zinc levels are associated with age related macular degeneration (AMD) leading to the emergence of zinc supplementation as a therapeutic choice for slowing the progression of the disease. There is however, no clear understanding of how this might be beneficial at the cellular level. In the present study we supplemented the drinking water of aged rats with zinc to monitor changes in gene expression in the eye.
Three groups of 10 month old female Long Evans rats were given supplemented drinking water for 8 months as follows: 1) normal lab water; 2) +10 mg/L zinc carbonate; and 3) +10 mg/L zinc carbonate + 0.2 mg/L copper carbonate. Following sacrifice at 18 months, one eye of each animal was used to isolate RNA for microarray analysis. Significant changes in gene expressions (p<0.05) were selected using Qlucore Omics Explorer and overrepresented pathways among regulated genes were selected using Ingenuity Pathway Analysis. Differential gene expressions were validated by real-time quantitative polymerase chain reaction. The fellow eyes were fixed for assessing morphological changes.
From the zinc affected genes 738 were represented in the Ingenuity database. Networks involved in oxidative stress, inflammatory response, DNA replication, recombination, and repair had high scores. Amongst the top molecular and cellular functions that were affected by zinc supplementation were: cell death, carbohydrate metabolism, small molecule biochemistry, cellular compromise and cell morphology. Previous work identified 114 RPE specific genes, via laser dissection of retinal cell layers and microarray analysis. Comparison of this list with our molecules resulted in a list of 15 overlapping molecules some of which are known to interact with zinc. There were no observed morphological changes.
Here, we show for the first time that oral zinc supplementation has the potential to invoke gene expression changes in the eye. This provides evidence that zinc can modify essential processes within the ocular tissue, the RPE cell layer in particular, to combat the major cause of blindness in the elderly. It is especially important to emphasize that our study was carried out on aged animals and for an extended period of time, mimicking closely the use of zinc supplementation in AMD.
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