April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
IKK2 Deletion in Macrophage Attenuates the Laser Induced Choroidal Neovascularization
Author Affiliations & Notes
  • Qiutang Li
    Ophthal and Visual Science, University of Louisville, Louisville, KY
    James Graham Brown Cancer Center, University of Louisville, Louisville, KY
  • Subhash Gaddipati
    Ophthal and Visual Science, University of Louisville, Louisville, KY
    James Graham Brown Cancer Center, University of Louisville, Louisville, KY
  • Ramesh B Kasetti
    Ophthal and Visual Science, University of Louisville, Louisville, KY
  • Henry J Kaplan
    Ophthal and Visual Science, University of Louisville, Louisville, KY
  • Qingxian Lu
    Ophthal and Visual Science, University of Louisville, Louisville, KY
    James Graham Brown Cancer Center, University of Louisville, Louisville, KY
  • Footnotes
    Commercial Relationships Qiutang Li, None; Subhash Gaddipati, None; Ramesh Kasetti, None; Henry Kaplan, None; Qingxian Lu, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 1264. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Qiutang Li, Subhash Gaddipati, Ramesh B Kasetti, Henry J Kaplan, Qingxian Lu; IKK2 Deletion in Macrophage Attenuates the Laser Induced Choroidal Neovascularization. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1264.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose: IKK2 is a key kinase in activation of transcriptional factor NF-kappaB that regulates multiple cellular processes including inflammation, stress response, cell death and angiogenesis. Neovascularization is a hallmark of wet AMD. We have previously showed that IKK2 inhibition in eye attenuates the laser-induced choroid neovascularization (CNV). In the current study, we further dissect the cellular and molecular mechanism of IKK2 involving the laser induced CNV formation.

Methods: (1) Examine the expression of molecular targets including VEGF, Hif1a, Ccl2, and Pdgfa in the RPE/Choroid/Sclera tissues obtained from vehicle- and TPCA-1(IKK2 inhibitor)-treated mice combined with or without laser injury. (2) Examine the effect of IKK2 inhibition on laser injury induced macrophage recruitment. (3) Examine the effect of macrophage specific deletion of IKK2 on laser -induced CNV formation The development of CNV after laser photocoagulation in TPCA-1-PLGA polymer treated mice and controls was quantified by scoring the fluorescence leakage and isolectin-B4-594 stain areas.

Results: NF-kappaB/IKK2 mediates CNV formation through controlling multiple pathways including inflammation, hypoxia response, and angiogenic factors. The laser induced macrophage recruitment was significantly reduced when IKK2 was inhibited. Furthermore, macrophage- specific deletion of IKK2 reduced laser induced CNV formation.

Conclusions: NF-kappaB/IKK2 regulates the CNV formation through targeting multiple signaling pathways including inflammation and hypoxia induced angiogenesis. IKK2-mediated inflammation and macrophage are critical players in the laser induced CNV. Our results suggest that IKK2 inhibition is a potential innovative therapeutic approach for treating wet AMD.

Keywords: 453 choroid: neovascularization • 557 inflammation • 412 age-related macular degeneration  
×
×

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.

×