April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
Immmunoregulatory Gene Profiling of Early and Late Induced Changes in Retinal Gene Expression After Intravitreal Steroid Injections in Mice
Author Affiliations & Notes
  • S. P. Modjtahedi
    Dept of Ophthalmology, University of California - Davis, Davis, California
  • Z. Smit-McBride
    Dept of Ophthalmology, University of California - Davis, Davis, California
  • C. Cessna
    Dept of Ophthalmology, University of California - Davis, Davis, California
  • K. Forward
    Dept of Ophthalmology, University of California - Davis, Davis, California
  • D. G. Telander
    Dept of Ophthalmology, University of California - Davis, Davis, California
  • L. M. Hjelmeland
    Dept of Ophthalmology, University of California - Davis, Davis, California
  • L. S. Morse
    Dept of Ophthalmology, University of California - Davis, Davis, California
  • Footnotes
    Commercial Relationships  S.P. Modjtahedi, None; Z. Smit-McBride, None; C. Cessna, None; K. Forward, None; D.G. Telander, None; L.M. Hjelmeland, None; L.S. Morse, None.
  • Footnotes
    Support  Grant: ALLERGAN RESEARCH FELLOWSHIP
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 1676. doi:
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      S. P. Modjtahedi, Z. Smit-McBride, C. Cessna, K. Forward, D. G. Telander, L. M. Hjelmeland, L. S. Morse; Immmunoregulatory Gene Profiling of Early and Late Induced Changes in Retinal Gene Expression After Intravitreal Steroid Injections in Mice. Invest. Ophthalmol. Vis. Sci. 2010;51(13):1676.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : To identify early and late changes in immunoregulatory gene expression pathways affected by intravitreal injections of triamcinolone acetonide (TA) and dexamethasone (Dex) in 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), group 3 (n=4) Dex (2µg). At 1day, 1 week and 1 month after the injections, the eyes were harvested for retinal dissection and total RNA isolation. Microarray analysis of 45,101 genes was performed using Affymetrix Mouse Genome 430 2.0. Statistically significant changes of immmunoregulatory genes of the eye were analyzed.

Results: : Intravitreal steroids cause a statistically significant change in expression of 1601 genes at 1 week and 1829 genes at 1 month. Looking at immunoregulatory and oxidative stress genes, we found that Dex and TA at 1 week post injection activates genes responsible for both anti-inflammatory actions and pro-inflammatory actions. For example, both Dex and TA up regulate interleukin-1 receptor (part of the cytokine signaling pathway) and transforming growth factor beta (an anti-inflammatory molecule). At one month, anti-inflammatory genes are predominantly activated--although there are differences between the steroids. For example, both Dex and TA up regulate interleukin-6 (a cytokine with anti-inflammatory actions), but only Dex down regulated tumor necrosis factor related protein 4.

Conclusions: : (i) microarray pathway analysis shows the full complexity of steroid effects on retinal gene expression.(ii) at early time points there is a mixture of pro-inflammatory and anti-inflammatory genes that are altered but at 1 month, anti-inflammatory gene activity predominates(iii) both steroids modulate immunoregulatory gene expression at one month, long after the steroid has been metabolized.(iv) differential gene expression may have clinical implications

Keywords: retina • gene microarray • injection 
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