July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Retinoid-regulated expression of pro-inflammatory cytokines in orbital tissues: a potential common denominator in orbital inflammatory syndromes.
Author Affiliations & Notes
  • Curtis J Heisel
    University of Michigan Medical School, Ann Arbor, Michigan, United States
  • Phillip E Kish
    Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan, United States
  • Niharika Rajesh
    LSA, University of Michigan, Ann Arbor, Michigan, United States
  • Alon Kahana
    Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan, United States
  • Footnotes
    Commercial Relationships   Curtis Heisel, None; Phillip Kish, None; Niharika Rajesh, None; Alon Kahana, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 1144. doi:https://doi.org/
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Curtis J Heisel, Phillip E Kish, Niharika Rajesh, Alon Kahana; Retinoid-regulated expression of pro-inflammatory cytokines in orbital tissues: a potential common denominator in orbital inflammatory syndromes.. Invest. Ophthalmol. Vis. Sci. 2018;59(9):1144. doi: https://doi.org/.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : Orbital tissues have a proclivity to inflame, particularly in the context of systemic inflammation, with severe consequences that can include blindness. Building on embryological research (1), we hypothesized that retinoids, transcriptional regulators uniquely enriched in orbital tissues (2), may play an important role in the pro-inflammatory milieu. We tested whether retinoids can regulate cytokine expression de novo, focusing on IL-1B and CCL2/MCP1 because of their known roles in thyroid eye disease and other orbital inflammatory conditions.
1. Bohnsack et al., Dev Biol, 2013
2. Sires et al., Arch Oph, 2001

Methods : Fibroblasts obtained from patients undergoing either orbital decompression (“thyroid eye disease”) or blepharoplasty (“normal”) were grown to confluence in primary tissue culture and then treated with combinations of all trans retinoic acid (ATRA) and 9-cis-RA (9CRA) at different concentrations. qRT-PCR was used to quantify expression of the cytokines CCL2 and IL-1B relative to the marker gene rps13.

Results : Treatment with 1.0M ATRA resulted in a higher mean relative expression (vs. DMSO control treatment) for CCL2 (n=33, 4.98 vs. 1.01, p<0.0001), IL-1B (n=28, 8.01 vs. 1.03, p<0.0001). Treatment with 9CRA resulted in a dose-dependent increase in mean relative expression of CCL2 (n=8, 1.0M=2.76, 0.3M=3.86, 0.1M=3.08, 0.03M=1.54), IL-1B (n-8, 1.0M=3.02, 0.3M=3.26, 0.1M=1.86, 0.03M=1.42), with 0.3M 9CRA inducing the highest relative expression for each cytokine. Treatment with a combination of 1.0M ATRA and four concentrations of 9CRA resulted in a higher mean relative expression than 9CRA alone for CCL2 (n=8, 1M 9CRA=6.17, 0.3M 9CRA=5.79, 0.1M 9CRA=4.43, 0.03M 9CRA=6.52) and IL-1B (n=8, 1M 9CRA =5.46, 0.3M 9CRA =5.12, 0.1M 9CRA =3.68, 0.03M 9CRA=6.94).

Conclusions : Our results reveal that the two retinoids tested are capable of inducing cytokine expression de novo, providing a preliminary explanation for the proclivity of orbital tissues to inflame. Importantly, the response to 9CRA was highly dose-dependent, with greater sensitivity in tissues from thyroid patients. The data suggest that there may be a synergistic effect of ATRA and 9CRA in inducing the expression of pro-inflammatory cytokines.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

 

Relative CCL2 & IL1B expression by treatment in patients with thyroid eye disease.

Relative CCL2 & IL1B expression by treatment in patients with thyroid eye disease.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×