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Y. Mitamura, C. Harada, T. Harada; Relationship of Nuclear Factor Kappa B to Monocyte Chemotactic Protein–1 Expression in the Pathogenesis of Proliferative Diabetic Retinopathy . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1726.
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© ARVO (1962-2015); The Authors (2016-present)
Molecular mechanism of epiretinal membranes (ERMs) formation in proliferative diabetic retinopathy (PDR) remains unclear. Monocyte chemotactic protein–1 (MCP–1) is one of the candidates responsible for recruiting macrophages into the eyes that has an important role in ERM formation. Because hyperglycemia condition induces MCP–1 expression under the control of transcription factor nuclear factor kappa B (NF–kB), we hypothesized a possibility that MCP–1 is regulated by NF–kB in PDR ERMs. Here, we examined colocalization of MCP–1 and NF–kB in PDR ERMs and performed in vitro studies.
ERM samples were obtained during vitrectomy from 5 eyes with PDR and processed for immunohistochemical analysis. After Mueller glial cells were stimulated with glycated albumin, nuclear localization of active form of NF–kB p50 was examined and MCP–1 levels were quantified by ELISA. To elucidate the importance of two NF–kB binding sites for MCP–1 transcriptional regulation, we performed luciferase assay.
Immunohistochemical analysis revealed that MCP–1 protein is colocalized with active form of NF–kB p50 in glial cell components of ERMs. In vitro studies demonstrated that glycated albumin induces NF–kB activation and up–regulation of MCP–1 production in retinal glial cells. Luciferase assay indicated that both of two NF–kB binding sites at the enhancer region are necessary for MCP–1 promoter activity.
These results suggest that MCP–1, under the regulation of NF–kB, is involved in the formation of ERMs following PDR.
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