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Sara P. Modjtahedi, Zeljka Smit-McBride, Albert K. Yu, David G. Telander, Leonard M. Hjelmeland, Lawrence S. Morse; To Identify Early And Late Changes In Immunoregulatory Gene Expression Pathways In Retinal Pigment Epithelium (RPE) Induced By Intravitreal Injections Of Triamcinolone Acetonide (TAA) And Dexamethasone (Dex) In The C57BL/6J Mice. Invest. Ophthalmol. Vis. Sci. 2011;52(14):27.
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To identify early and late changes in immunoregulatory gene expression pathways in retinal pigment epithelium (RPE) induced by intravitreal injections of triamcinolone acetonide (TAA) and dexamethasone (Dex) in the C57BL/6J mice.
All research was conducted in compliance with the ARVO statement for the use of animals. Intravitreal injections were performed transconjunctivally in anesthetized C57BL/6J mice with Hamilton 33g needles delivering 2 ul of solution. In group 1 (n=4) animals received balanced intravitreal salt solution (BSS), group 2 (n=4) TA (20µg), and in group 3 (n=4) Dex (2µg). At 1 week and 4 weeks after the injections, the eyes were harvested for RPE dissection and total RNA isolation. Microarray analysis of 45,101 genes was performed using Affymetrix Mouse Genome 430 2.0. Statistically significant changes of immunoregulatory genes of the eye were analyzed.
Specifically looking at immunoregulatory genes at 1 week post-injection, we found that both Dex and TAA induce changes in genes responsible for both anti- and pro-inflammatory actions. For example, Dex up-regulates the IL-1 receptor, down regulates chemokine receptor 5, and down regulates IL-17. TAA at 1 week up-regulates IL-1beta , down regulates the IL-1 receptor, and down regulates IL-4. However, TAA also down- regulates several interferon-related genes and chemokines involved in inflammation. At 4 weeks Dex down-regulates IL10, up-regulates toll-like receptor 7 (a molecule that mediates cytokine production), and up-regulates interferon regulatory factor 3. TAA at 4 weeks down-regulates IL-6, a known critical pluripotent immune mediator in the eye.
(i) Microarray pathway analysis shows that two similar steroids display differential gene activation changes in same and overlapping biological pathways, but affect distinct sets of RPE genes. (ii) At both time points there is a mixture of pro-inflammatory and anti-inflammatory RPE genes that are altered with TAA and Dex. (iii) Understanding differential gene expression may have clinical implications.
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