April 2011
Volume 52, Issue 14
ARVO Annual Meeting Abstract  |   April 2011
Analysis of the Differential Potential of TLRs to Elicit Uveitis in Mice
Author Affiliations & Notes
  • Stephen R. Planck
    Casey Eye Institute, Oregon Health & Science Univ, Portland, Oregon
  • Jordan J. Allensworth
    Casey Eye Institute, Oregon Health & Science Univ, Portland, Oregon
  • James T. Rosenbaum
    Casey Eye Institute, Oregon Health & Science Univ, Portland, Oregon
  • Holly L. Rosenzweig
    Casey Eye Institute, Oregon Health & Science Univ, Portland, Oregon
  • Footnotes
    Commercial Relationships  Stephen R. Planck, None; Jordan J. Allensworth, None; James T. Rosenbaum, None; Holly L. Rosenzweig, None
  • Footnotes
    Support  NIH EY019020, NIH EY019604; American College of Rheumatology Research Foundation (HLR.) and Research to Prevent Blindness Awards (HLR and the Casey Eye Institute.)
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 2269. doi:
  • Views
  • Share
  • Tools
    • Alerts
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Stephen R. Planck, Jordan J. Allensworth, James T. Rosenbaum, Holly L. Rosenzweig; Analysis of the Differential Potential of TLRs to Elicit Uveitis in Mice. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2269.

      Download citation file:

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

  • Supplements

Purpose: : Toll-like receptors (TLRs) are critical to host defense and innate immunity. Not only are TLRs important in microbial defense but emerging evidence supports their role in many chronic, inflammatory diseases. The eye is uniquely sensitive to the TLR4 agonist, LPS, and LPS-induced uveitis has been well-established in various rodent models. How activation of other TLRs may influence the onset and/or severity of uveitis has not been thoroughly examined. Here, we systematically examined the inflammatory potential of 9 TLRs (TLR1/2, TLR2/6, TLR3, TLR4, TLR5, TLR7/8, and TLR9) for their ability to trigger uveitis in mice.

Methods: : Female, age-matched BALB/c mice were administered intravitreal injections of the following synthetic TLR agonists: Pam3CSK4 (TLR2/1), FSL-1 (TLR2/6), Poly(I:C) (TLR3), lipid A (TLR4), flagellin (TLR5), R848 (TLR7/8) and CpG ODN (TLR9). The contralateral eye was intravitreally injected with saline or appropriate peptide or nucleic acid controls. The leukocytic response within the vasculature and extravascular tissue of the iris was assessed using intravital videomicroscopy over the first 24 h following injections. The inflammatory potential of TLR agonists was also assessed in iris or retina explant cultures. Cytokine production within the supernatants was then quantified by Luminex-ELISA at 24 h post stimulation.

Results: : Iris or retina explants directly stimulated with various TLR agonists demonstrated marked increase in production of inflammatory cytokines (IL-6, IP-10/CXCL10, KC, MCP-1, and RANTES) but relatively little production of IFNγ, IL-12p70, IL-10, IL-1β, IL-4 or TNFα). Some unique cytokine profiles were noted. For example Poly(I:C) (TLR3 agonist) triggered greater amounts of IP-10 production compared to TLR2 agonists (Pam3CSK4 or FSL1). Overall, iris tissue was more sensitive to TLR stimulation than retina tissue. Despite the ability of all TLR agonists tested to elicit cytokine production in iris explants, the inflammatory potential of TLR agonists differed greatly when administered locally to the eye. For example, Poly(I:C) (TLR3 agonist) was a very poor trigger of uveitis compared to CpG ODN (TLR9 agonist), lipid A (TLR4 agonist) or TLR2 agonists.

Conclusions: : Our data provide insight into how activation of different TLRs may predispose to uveitis in mice. Intriguingly, despite comparable TLR-triggered cytokine production in vitro, the in vivo responses were more variable.

Keywords: uveitis-clinical/animal model • inflammation • cytokines/chemokines 

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.