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John C. Lang, Alison Ziesel, Daniel T. Organisciak, Christine Rapp, Ruth Darrow, Rekha Rangarajan, Paul Wong; Zinc Modulates The Genetic Signature Of The Retina In Response To Acute Light Exposure. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2589.
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© ARVO (1962-2015); The Authors (2016-present)
Zinc is a component in an AREDS formulation for AMD treatment and effectively protects against acute light induced retinal degeneration, LIRD (Organisciak et al., ARVO 2011: 4423). How zinc mediates this effect is not understood. Gene profiling studies were performed to examine if zinc directly mediates changes in retinal gene expression.
Sprague Dawley rats were exposed to 4 treatment conditions (vehicle (VEH) or zinc oxide (ZN, 5.2 mg/kg), with (LT) or without (NOLT) 4 h intense light exposure (1200 lux; 490-580 nm)). A 4 h light exposure defines an early time point in the LIRD process. The ZN dose used is known to provide protection from LIRD. Retinas were taken 5 h after VEH or ZN treatment and flash frozen. Total RNA was extracted and RNA samples were used to initiate screens of Illumina rat gene expression arrays (Illumina, San Diego, CA). Each array allows the screening of 22,525 gene marker loci. 3 arrays were screened per treatment condition using independent samples. Expression data was analyzed with Illumina Genome/ Bead Studio software, lumi and limma. Additional informatic analyses of gene lists derived from these analyses were performed with IPA software (Ingenuity Systems, Redwood City, CA).
Three differential screens were run (1: ZN NOLT X VEH NOLT; 2: ZN LT X ZN NOLT; 3:VEH LT X VEH NOLT). The gene profiles between the two NOLT treatments are similar, with only 9 genes screened proving to be differential. 871 and 662 differential expressed annotated genes were identified in screen 2 and 3 respectively. Among these genes, 401 define light induced changes (genes with the same response to LT regardless of a ZN or VEH pretreatment) and 730 genes that define zinc influenced changes.
Zinc does not seem to have much of a direct effect on retinal gene expression in the absence of intense light. It does however seem to modulate the retinal response to light exposure and in this way has an unexpected hand in changing the genetic signature. 535 of the ZN modulated (directly or indirectly) genes identified were annotated in the Ingenuity biofunction/ontology database, 338 of these (63%) fall into a network of cell death, cell growth, and cell cycle related genes and it may be that the subtle augmentation of these networks is key to the protection from LIRD.
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