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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.
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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.
(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.
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.
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.
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