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J.-W. Jang, H. Lim, H. Kim, Y. Cho, D.-S. Kim; EG-Mirotin® Accelerates Pericytes Coverage And Astrocytes Interaction. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3313.
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© ARVO (1962-2015); The Authors (2016-present)
EG-Mirotin® is a novel therapeutics for diabetic retinopathy. We investigated the therapeutic effects and mechanisms of EG-Mirotin® using oxygen induced retinopathy (OIR) model. It was assessed in a viewpoint of histopathology; pericyte coverage, astrocyte recruitment and vascular network remodeling.
OIR was induced in C57BL/6 mice by exposure to 75% oxygen. OIR and control pups respectively received EG-Mirotin® (10 ug/kg/day, intraperitoneal) and saline for 5 days. The vascular responses were examined immunocytochemically using retinal wholemounts labeled with endothelial (Isolectin-B4), pericyte (NG2) markers and systemic perfusion with fluorescence dye (FITC).
OIR resulted in the increase of dysfunctional vessels and avascular areas in retina. Central and mid-peripheral vessels in OIR retina were not or partially perfused, thus it was induced broad avascular lesions. Meanwhile, the administration of EG-Mirotin® in OIR mice showed a decrease of retinopathy score and avascular area. In isolectin-B4 and FITC double staining, the number of non-functional vessels, which stained with isolectin-B4 but were not perfused by FITC, was decreased by EG-Mirotin®. The shape of retinal vascular networks was changed closely to normal in the cohort. Pericytes, found in close proximity to vessels, were hardly observed in the central inner layer of OIR retina. Peri- and inter-vascular distribution of astrocyte also rarely observed in the same area. However, the vessels, distributed in an inner retina, of EG-Mirotin® treated retina were completely covered by pericytes and interacted with the many processes of astrocyte. Pericyte ensheathment and astrocyte interaction with micro-vessels in EG-Mirotin® treated retina were quantitatively similar with normal retina.
It is the histopathological features of OIR that abnormal vascular morphology, poor pericyte-endothelial interactions and astrocyte degenerations. The treatment of EG-Mirotin® in OIR leads astrocytes induction to central proliferating retina, and then they restore the intraretinal vasculature and induce the mature vessels by pericyte ensheathment at the same time. As a result, EG-Mirotin® induced the reconstruction of vascular networks and the improvement of blood flow in OIR retina. This study indicates a rationale for additional investigation of EG-Mirotin® into the potential clinical benefit of pharmacological manipulation in the treatment of ischemic disease.
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