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Atsuhiro Kanda, Yoko Dong, Kousuke Noda, Wataru Saito, Susumu Ishida; Advanced Glycation End Products Link Inflammatory Response to Upregulation of Galectin-1 in Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5206.
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Galectin-1, a galactoside-binding lectin protein, has recently been shown to increase in the vitreous of proliferative diabetic retinopathy (DR) eyes independently of vascular endothelial growth factor (VEGF) and to co-localize with VEGFR2 in fibrovascular tissues. Galectin-1 application to endothelial cells causes VEGFR2 phosphorylation and in vitro angiogenesis. In this study, to understand the contribution of galectin-1 to the pathogenesis of DR, we investigated regulatory mechanisms of galectin-1 in vitro and in vivo.
Human surgical samples were examined by enzyme-linked immunosorbent assay and immunofluorescence. Immunoblot analysis and real-time PCR were performed to measure protein and mRNA expression levels in several human cell lines and streptozotocin-induced diabetes in mice.
Galectin-1 protein levels in aqueous humor samples increased with the progression of clinical stages of DR. In vitro, administration with advanced glycation endproducts (AGEs) to macrophages induced proinflammatory cytokine interleukin (IL)-1β production via toll-like receptor 4, and IL-1β stimulation elevated galectin-1/LGALS1 expression in Müller glial cells. Intravitreal injection of anti-Il-1β neutralizing antibody significantly decreased galectin-1/Lgals1 expression in diabetic mice.
We propose that AGEs produced in diabetes activate inflammatory cascades in macrophages followed by Müller glial cells, leading to an increase in galectin-1. Our findings reveal for the first time the significant involvement of galectin-1 in the pathogenesis of DR along with the degree of disease severity.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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