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H. Takahashi, R. Obata, Y. Yanagi, Y. Tamaki, Y. Terauchi, T. Kadowaki; Influence of Insulin Receptor Substrate–2–Knockout on the Activity of Experimental Choroidal Neovascular in Mice Model . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2595.
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© ARVO (1962-2015); The Authors (2016-present)
Insulin receptor substrate–2 (IRS–2) is one of the intracellular molecules acting downstream of insulin receptor signaling pathway. Although previous investigators implicated that insulin is involved in the pathogenesis of choroidal neovascularization (CNV) in age–related macular degeneration, little is known about the underling molecular mechanism. In this study, to investigate the possible influence of IRS–2 on CNV activity, CNV model was created in mice lacking IRS2 gene (Irs –/– mice).
Irs2–/– mice with C57BL/6 background aging 50 weeks were used in this study. CNV was induced by diode laser–photocoagulation (Spot size 200mm, exposure time 0.01 seconds, power 220mW) in the right eyes of these mice. Five days thereafter, fluorescein angiography was performed to evaluate the leakage from CNV. To calculate the integrated lesion intensity (ILI) reflecting the integrated lesion hyperfluorescence from the photocoagulated lesions, fluorescein angiographic images at 4 to 6 minutes after the injection were digitized and analyzed by NIH software. The ILIs were averaged to give the value for one mouse. Fluorescein angiography was performed with the observer masked as to treatment.
Fluorescein leakage from the CNV lesions had increased by 49% in the eyes of Irs–/– mice compared to the leakage in the wild–type mice (p=0.0399). Fluorescein leakage from Irs+/– mice CNV lesions tended to increase, but not significantly, compared to the leakage in the wild–type mice.
Loss of IRS–2 gene results in CNV activation, suggesting that IRS–2 inhibits CNV leakage and/or growth.
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