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Z. Smit-McBride, L. S. Morse, C. Cessna, D. G. Telander, S. S. Park, L. M. Hjelmeland; Global Gene Profiling of Early and Late Induced Changes in Gene Expression Upon Intravitreal Injection of Triamcinolone and Dexamethasone in the Mouse Retina. Invest. Ophthalmol. Vis. Sci. 2009;50(13):494.
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© ARVO (1962-2015); The Authors (2016-present)
To identify gene expression pathways affected by intravitreal injections of Triamcinolone Acetonide (TA) and Dexamethasone (Dex) at 1 week and 1 month in the C57BL/6J mouse eye.
All research was conducted in compliance with the ARVO statement for the use of animals in ophthalmic and vision research. Intravitreal injections were performed transconjunctivally in anesthetized C57BL/6J mice with Hamilton syringes and 33g needles delivering 2 ul of solution according to institutional protocol. In group 1 (n=8) animals received balanced intravitreal salt solution (BSS), in group 2 (n=8) TA (20µg), in group 3 (n=8) Dex (2µg). At 1 week and 4 weeks after the injections, 4 mice from each group were sacrificed by pentobarbital sodium overdose (120mg/kg) and the eyes were harvested for retinal dissection and total RNA isolation. Microarray analysis of 45,101 genes was performed using Affymetrix MOE-430-2 GeneChip arrays. Data analysis was performed using Affymetrix Expression Console, GeneSpring GX, and Ingenuity Pathway (IPA) software.
Preliminary data analysis showed that two treatments at 1 week post injection displayed differential gene expression changes in overlapping biological pathways, but affecting distinct sets of genes. Furthermore, preliminary results suggest to be a difference between set of genes that are expressed at 1 week and 4 weeks post-injection. Major Gene Ontology (GO) biological processes of interest that were rated as significantly different between three experimental groups by parametric Welch ANOVA test were regulation of apoptosis, angiogenesis, intracellular signaling cascades and transcriptional regulation.
Microarray pathway analysis shows full complexity of TA and Dex effects on retinal gene expression in the C57BL/6J mouse eye. It appears that they have several biological processes in common (apoptosis, inflammatory response, etc.) that are downregulated, but it appears that they are using slightly different pathways, and/or different members of the gene families. Different gene expression pattern from 1 week and 1 month post-treatment was observed. Understanding differential gene expression may have pharmacogenomic and clinical implications.
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