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S. Yamasaki, E. Sakurai, K. Yamada, M. Itaya, J. Ambati, Y. Ogura; Anti–Angiogenic Effect of Recombinant Interleukin–10 on Experimental Choroidal Neovascularization . Invest. Ophthalmol. Vis. Sci. 2006;47(13):904.
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© ARVO (1962-2015); The Authors (2016-present)
Interleukin–10 (IL–10) is an immunosuppressive cytokine and is drawing attention as an inhibitor of tumor angiogenesis. Additionally, IL–10 is a potent inhibitor of monocyte macrophage activation. We investigated whether IL–10 inhibits choroidal neovascularization (CNV).
CNV was induced by laser injury in C57BL/6J and area measured 7days later by confocal evaluation of Griffonia simplicifolia Isolectin B4 staining of RPE–choroid flat mounts. Recombinant IL–10 or control antibodies were injected into the vitreous immediately after the laser injury. IL–10 and VEGF levels in the RPE/choroid were measured by ELISA, and quantified macrophage infiltration into the choroid was analyzed by flow cytometry staining with F4/80.
Intravitreous injection of recombinant IL–10 significantly reduce CNV (51.7±5.3%; P<0.001) compared to the control. In the results of the control FACS using F4/80, laser injury recruited macrophage infiltration into the choroid, peaking 3 days after injury. And there was significant suppression of quantified macrophage infiltration into the choroid in the IL–10 treated group (48.4±7.8%; P<0.001) compared to the control 3 days after the laser injury. The VEGF level was significantly reduced (64.5±12.5%; P<0.001) in the IL–10 treated group. IL–10 was not expressed in the control RPE/choroid following the laser injury from Day 1 through Day 7.
IL–10 had not been shown to upregulate during angiogenic process in laser induced CNV. However, intravitreous injection of IL–10 had suppressive effects on the angiogenesis in the experimental CNV, possibly by the inhibition of recruitment and activation macrophage. Although the mechanisms of the antiangiogenic effect of IL–10 are still unclear, the potential usefulness of IL–10–mediated gene therapy of CNV was suggested.
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