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Mohamed Al-Shabrawey, Sylvia Megyerdi, Pamela Martin, Nader Sheibani, Stephen Hsu; Caspase-14 Expression Impairs Retinal Pigment Epithelial Cell Barrier Function. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1198.
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We recently showed that caspase-14 is a novel molecule in the retina that could a potential player in the pathogenesis of diabetic retinopathy. Its specific functional role has yet to be elucidated, but we have evidence that function could vary from cell species. Previously, we have shown that caspase-14 plays a role in the pathogenesis of DR by accelerating retinal pericytes and endothelial cell death in vitro. However, we have new evidence that suggests that in addition caspase-14 might be involved in retinal pigment epithelium cell barrier function.
Caspase-14 transfected ARPE-19 cells were evaluated for changes in the barrier function using FITC-Dextran Flux assay and phagocytic activity using a special phagocytic assay kit (pHrodo Red E.coli BioParticles Conjugate). Expression of the apoptotic marker caspae-3 and PARP-1 and the pro-inflammatory caspase-4 was also examined using Western blotting.
In caspase-14 transfected ARPE-19 cells, there was significant increases in the FITC-dextran permeability throught cultured retinal endothelial cell confluent monolayer compared to the control cells (P<0.05). This was associated with marked increase in the caspase-4 expression. However, no significant changes were evident in the phagocytic activity or the apoptotic caspase-3 and PARP1.
Caspase-14 is implicated in the inflammatory response by RPE rather than apoptosis or phagocytic activity. These findings suggest caspase-14 as a potential player and target in diseases associated with disrupted RPE barrier function such as age-related macular degeneration and macular edema.
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