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Qiutang Li, Huayi Lu, Wei Wang, Qingxian Lu, Henry J. Kaplan; Ikk2 Inhibition Attenuates The Laser Induced Choroidal Neovascularization. Invest. Ophthalmol. Vis. Sci. 2012;53(14):5832.
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© ARVO (1962-2015); The Authors (2016-present)
NF-kappaB is a transcription family that regulates multiple cellular processes including inflammation, stress response, cell death and tumor angiogenesis. IKK2 is a key kinase to regulate NF-kappaB activity. In this study we investigated the effect of IKK2 inhibition on laser-induced choroid neovascularization (CNV).
We established the mouse model where the retinal neuronal tissue specific deletion of IKK2 is achieved by mating mice IKK2-/flox carrying one IKK2 mutant allele and one IKK2-flox allele with the mouse line expressing Cre recombinase under control of Nestin promoter. We examined the retina specific deletion of IKK2 by examining mRNA and protein levels. The role of IKK2 in retina development was evaluated by immunohistology examination of eye sections and further functionally tested by optokinetic reflex (OKR). Pathological neovascularization is a hallmark of late stage neovascular (wet) age-related macular degeneration (AMD) and CNV could be induced by laser damage. The pathologic changes in response to laser damage in IKK2 deficient retina were compared with normal control animals. The development of CNV after laser photocoagulation was quantified by scoring the fluorescence leakage and dextrain stain areas and measuring the thickness of choroidal neovascular membrane. Furthermore, the effect of IKK2 inhibitor TPCA-1 on the development of laser-induced CNV was investigated after intravitreal and retrobulbar administration into mouse eye.
Our results showed that IKK2 was efficiently knocked out from the retinas in the IKK2Fl/-/Nestin-Cre mice. Lacking of IKK2 did not affect the retina development and function. However, there was a significant reduction in the choroidal neovascularization after laser induction in IKK2Fl/-/Nestin-Cre mice. In addition, laser-induced choroid neovascularization was significantly attenuated by intravitreal and retrobulbar injection of IKK2 specific chemical inhibitor TPCA-1. Local TPCA-1 administration at the experimental dosage did not affect the visual function.
IKK2 plays a role during choroidal neovascularization processes and IKK2 inhibition can attenuate the laser-induced CNV development. Our results suggest IKK2 inhibition is a promising therapeutic approach for Age-related macular degeneration.
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