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Hidetaka Noma, Kevin McDonald, Masahiko Shimura, Shigeo Tamiya; MCP-1 disrupts morphologic and functional barrier properties of polarized retinal pigment epithelium. Invest. Ophthalmol. Vis. Sci. 2017;58(8):598.
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© ARVO (1962-2015); The Authors (2016-present)
Retinal pigment epithelial (RPE) cells form the blood-ocular barrier, and their polarized property is crucial for maintaining the barrier function. Loss of RPE barrier function is associated with variety of ocular disorders. The expression of monocyte chemoattractant protein (MCP)-1, an inflammatory cytokine, is increased in several diseases in which RPE barrier function is likely disrupted. We hypothesized that MCP-1 is involved in this process, and the purpose of this study was to investigate the effects of MCP-1 on the barrier function of polarized RPE cells.
Isolated porcine RPE cells were seeded on Transwell™ membranes. Transepithelial electrical resistance (TER) was measured using EVOM (WPI). Polarized RPE (TER >150 Ω cm2) cells were incubated with 10 ng/ml or 20 ng/ml of MCP-1 and the TER was measured. The sites of the tight junction-associated molecules ZO-1, claudin-19, and F-actin were determined immunohistochemically.
MCP-1 significantly decreased the TER of polarized RPE cells in both 10 ng/ml and 20 ng/ml compared to controls at 24 hours. Immunohistochemical staining revealed that claudin-19 located between cells in control RPE cells was disassembled by MCP-1. Interestingly, in contrast, ZO-1 remained intact in the presence of MCP-1.
These findings suggest that MCP-1 can breakdown RPE barrier function in polarized RPEs by disassembling claudin-19. MCP-1, therefore, might play an important role in ocular disorders with disrupted barrier function.
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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