Inhibition of acetylcholinesterase attenuated retinal inflammation via suppressing NF- κB activation.

This study was aimed to dissect the role of ACHE in retinal inflammation, and its mechanism of action. Retinal inflammation was induced by intravitreal injection of tumor necrosis factor-α (TNF-α) in heterozygous ACHE knockout mice (ACHE+/-) and wild type mice (ACHE+/+). Donepezil, a well-known ACHE inhibitor, was administrated by daily gavage. Expression of ACHE and intercellular adherent molecule-1 (ICAM-1), infiltration of CD11b+ inflammatory cells, retinal leukostasis and vascular leakage was determined in both ACHE ± and ACHE+/+ mice. ARPE-19 cells, a human retinal pigment epithelial cell line, were cultured for in vitro assay. Knockdown of ACHE was achieved by lipofectamine-mediated siRNA transfection and pharmaceutical suppression of ACHE was manipulated by donepezil. Cellular expression and distribution of ACHE, ICAM-1, and phosphorylation of NF-κB, IκB and IKKα/β were detected by western-blot analysis or immunocytochemistry. Retinal expression of ACHE was dramatically upregulated, in parallel with increased ICAM-1 expression, enhanced leukostasis and augmented CD11b+ inflammatory cells infiltration as well as vascular hyperpermeability in ACHE+/+ mice injected with TNF-α. However, TNF-α-injected ACHE ± mice showed lower level of ICAM-1, less leukostasis and fewer infiltrated CD11b+ cells. Moreover, TNF-α-induced retinal vascular leakage was significantly reduced in ACHE ± mice. Similarly, TNF-α-induced retinal inflammatory response were also attenuated...
Source: Experimental Eye Research - Category: Opthalmology Authors: Tags: Exp Eye Res Source Type: research