April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
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
Author Affiliations & Notes
  • Sara P. Modjtahedi
    Dept of Ophthalmology, University of California - Davis, Davis, California
  • Zeljka Smit-McBride
    Dept of Ophthalmology, University of California - Davis, Davis, California
  • Albert K. Yu
    Dept of Ophthalmology, University of California - Davis, Davis, California
  • David G. Telander
    Dept of Ophthalmology, University of California - Davis, Davis, California
  • Leonard M. Hjelmeland
    Dept of Ophthalmology, University of California - Davis, Davis, California
  • Lawrence S. Morse
    Dept of Ophthalmology, University of California - Davis, Davis, California
  • Footnotes
    Commercial Relationships  Sara P. Modjtahedi, None; Zeljka Smit-McBride, None; Albert K. Yu, None; David G. Telander, None; Leonard M. Hjelmeland, None; Lawrence S. Morse, None
  • Footnotes
    Support  Allergan Fellowship Grant and Research to prevent blindness
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 27. doi:
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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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Abstract

Purpose: : 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.

Methods: : 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.

Results: : 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.

Conclusions: : (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.

Keywords: retinal pigment epithelium • gene/expression • injection 
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