2024-03-29T14:50:02Zhttps://eprints.lib.hokudai.ac.jp/dspace-oai/requestoai:eprints.lib.hokudai.ac.jp:2115/763012022-11-17T02:08:08Zhdl_2115_20040hdl_2115_121Unsaturated Aldehyde Acrolein Promotes Retinal Glial Cell Migration1000050423752Murata, Miyuki1000090296666Noda, KousukeYoshida, ShihoSaito, MichiyukiFujiya, Akio1000080342707Kanda, Atsuhiro1000010245558Ishida, Susumumetadata only accessCreative Commons Attribution-NonCommercial-NoDerivatives 4.0 InternationalAcroleinCXCL1oxidative stressMuller cell490PURPOSE. To investigate the effect of the unsaturated aldehyde acrolein on retinal glial cell migration. METHODS. Muller glial cell markers expression in TR-MUL5 were confirmed by RT-PCR and immunostaining. Cell viability and migration rate of TR-MUL5 cells were assessed after the stimulation with acrolein. DNA microarray analysis was performed to analyze changes in the expression levels of migration-related genes in Muller glial cells stimulated with acrolein. Real-time PCR and ELISA were performed to validate DNA microarray analysis results. Inhibitors of C-X-C motif chemokine ligand 1 (CXCL1), one of the genes highly upregulated after the exposure to acrolein, and blockers of its receptor, CXCR2, were used to investigate the role of the CXCL1-CXCR2 axis on glial cell migration. CXCL1 concentration was measured in vitreous fluid samples obtained from proliferative diabetic retinopathy (PDR) and nondiabetic control eyes. CXCL1 and CXCR2 expression in glial cells of fibrovascular tissues obtained from PDR patients was examined by immunostaining. RESULTS. At a high concentration, acrolein (100 mu M) significantly decreased cell viability. However, in moderate, sublethal concentrations (25-50 mu M), acrolein induced cell migration and substantially increased the production of CXCL1 in TR-MUL5 cells. CXCL1 concentration was significantly elevated in vitreous fluids of PDR patients, and CXCL1 and CXCR2 were present in glial cells in fibrovascular tissues of PDR patients. CXCL1 stimulation increased glial cell migration in a dose-dependent manner, which was abrogated by the neutralization of the CXCL1-CXCR2 axis. CONCLUSIONS. Our data demonstrate that acrolein promotes retinal Muller glial cell migration by enhancing CXCL1 production.Association for Research in Vision and Ophthalmology(ARVO)2019-10engjournal articleNAhttp://hdl.handle.net/2115/76301https://doi.org/10.1167/iovs.19-273460146-0404Investigative ophthalmology & visual science601344254435