Yukihiko Suzuki1, Mitsuru Nakazawa2, Kaori Suzuki2, Hitoshi Yamazaki2, Yasuhiro Miyagawa2. 1. Department of Ophthalmology, Hirosaki University Graduate School of Medicine, 5 Zaifu, Hirosaki, Aomori, 036-8562, Japan. yukihiko@cc.hirosaki-u.ac.jp. 2. Department of Ophthalmology, Hirosaki University Graduate School of Medicine, 5 Zaifu, Hirosaki, Aomori, 036-8562, Japan.
Abstract
PURPOSE: The involvement of cytokines and chemokines in vitreous fluid is important in the development and progression of diabetic retinopathy (DR) and central retinal vein occlusion (CRVO). In this study, the concentrations of cytokines and chemokines in the vitreous fluid of eyes with DR and CRVO were measured and compared. METHODS: We studied 76 eyes with proliferative DR and diabetic macular edema (DR group), 10 eyes with CRVO (CRVO group), and 23 eyes with an epiretinal membrane and macular hole (control group), among a series of 160 eyes from which vitreous fluid samples were collected during vitrectomy. The vitreous fluid samples were collected by suction with a vitreous cutter at the initial stage of vitrectomy. Twenty-seven different cytokines and chemokines were measured simultaneously using an array system (Bio-Plex(®)) with beads combined with antibodies (Bio-Rad), as follows: interleukin (IL)-1β, IL-1 receptor agonist, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12, IL-13, IL-15, IL-17, eotaxin, basic fibroblast growth factor, granulocyte colony-stimulating factor (G-CSF), granulocyte/macrophage colony-stimulating factor (GM-CSF), interferon (IFN)-γ, interferon-inducible 10-kDa protein (IP-10), monocytochemotactic protein-1 (MCP-1), macrophage inflammatory protein-1 alpha (MIP-1α), MIP-1β, platelet-derived growth factor (PDGF)-BB, regulated upon activation, normal T cell expressed and secreted, tumor necrosis factor alpha (TNF-α), and vascular endothelial growth factor (VEGF). RESULTS: Compared to the control group, the levels of IL-6, IL-8, IL-10, IL-13, IP-10, MCP-1, MIP-1β, PDGF and VEGF in the vitreous fluid were significantly higher in the DR group, while the levels of IL-1β, IL-2, IL-5, IL-8, IL-9, IL-10, IL-12, IL-13, eotaxin, G-CSF, IFN-γ, IP-10, MCP-1, MIP-1β, TNF-α and VEGF were significantly higher in the CRVO group. Compared to the DR group, IL-2, IL-9, IL-12, MCP-1 and IFN-γ were significantly elevated in the CRVO group. Multivariate regression analysis revealed that among 6 factors correlated to VEGF in the DR group, IL-10 and IL-13 were more positively correlated and PDGF was most inversely correlated to VEGF. CONCLUSION: In addition to inflammatory cytokines and neurotrophic factors such as VEGF, anti-inflammatory cytokines such as IL-10 and IL-13 may be involved more in the pathogenesis of DR and CRVO than in other diseases; cytokines and chemokines may also be correlated to VEGF in the vitreous fluid. It is also suggested that the inflammatory reaction may be more activate in CRVO than in DR.
PURPOSE: The involvement of cytokines and chemokines in vitreous fluid is important in the development and progression of diabetic retinopathy (DR) and central retinal vein occlusion (CRVO). In this study, the concentrations of cytokines and chemokines in the vitreous fluid of eyes with DR and CRVO were measured and compared. METHODS: We studied 76 eyes with proliferative DR and diabetic macular edema (DR group), 10 eyes with CRVO (CRVO group), and 23 eyes with an epiretinal membrane and macular hole (control group), among a series of 160 eyes from which vitreous fluid samples were collected during vitrectomy. The vitreous fluid samples were collected by suction with a vitreous cutter at the initial stage of vitrectomy. Twenty-seven different cytokines and chemokines were measured simultaneously using an array system (Bio-Plex(®)) with beads combined with antibodies (Bio-Rad), as follows: interleukin (IL)-1β, IL-1 receptor agonist, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12, IL-13, IL-15, IL-17, eotaxin, basic fibroblast growth factor, granulocyte colony-stimulating factor (G-CSF), granulocyte/macrophage colony-stimulating factor (GM-CSF), interferon (IFN)-γ, interferon-inducible 10-kDa protein (IP-10), monocytochemotactic protein-1 (MCP-1), macrophage inflammatory protein-1 alpha (MIP-1α), MIP-1β, platelet-derived growth factor (PDGF)-BB, regulated upon activation, normal T cell expressed and secreted, tumor necrosis factor alpha (TNF-α), and vascular endothelial growth factor (VEGF). RESULTS: Compared to the control group, the levels of IL-6, IL-8, IL-10, IL-13, IP-10, MCP-1, MIP-1β, PDGF and VEGF in the vitreous fluid were significantly higher in the DR group, while the levels of IL-1β, IL-2, IL-5, IL-8, IL-9, IL-10, IL-12, IL-13, eotaxin, G-CSF, IFN-γ, IP-10, MCP-1, MIP-1β, TNF-α and VEGF were significantly higher in the CRVO group. Compared to the DR group, IL-2, IL-9, IL-12, MCP-1 and IFN-γ were significantly elevated in the CRVO group. Multivariate regression analysis revealed that among 6 factors correlated to VEGF in the DR group, IL-10 and IL-13 were more positively correlated and PDGF was most inversely correlated to VEGF. CONCLUSION: In addition to inflammatory cytokines and neurotrophic factors such as VEGF, anti-inflammatory cytokines such as IL-10 and IL-13 may be involved more in the pathogenesis of DR and CRVO than in other diseases; cytokines and chemokines may also be correlated to VEGF in the vitreous fluid. It is also suggested that the inflammatory reaction may be more activate in CRVO than in DR.
Authors: J Fernando Arevalo; Jans Fromow-Guerra; Hugo Quiroz-Mercado; Juan G Sanchez; Lihteh Wu; Mauricio Maia; Maria H Berrocal; Adriana Solis-Vivanco; Michel E Farah Journal: Ophthalmology Date: 2007-04 Impact factor: 12.079
Authors: L P Aiello; R L Avery; P G Arrigg; B A Keyt; H D Jampel; S T Shah; L R Pasquale; H Thieme; M A Iwamoto; J E Park Journal: N Engl J Med Date: 1994-12-01 Impact factor: 91.245
Authors: Ming-Shih Hwang; Michael G Strainic; Elliot Pohlmann; Haesuk Kim; Elzbieta Pluskota; Diana L Ramirez-Bergeron; Edward F Plow; M Edward Medof Journal: J Cell Sci Date: 2019-03-28 Impact factor: 5.285
Authors: Dan-Ning Hu; Mingchao Bi; David Y Zhang; Fei Ye; Steven A McCormick; Chi-Chao Chan Journal: Invest Ophthalmol Vis Sci Date: 2014-08-14 Impact factor: 4.799
Authors: Alex Yuan; Baseer U Ahmad; David Xu; Rishi P Singh; Peter K Kaiser; Daniel F Martin; Jonathan E Sears; Andrew P Schachat; Justis P Ehlers Journal: Int J Ophthalmol Date: 2014-02-18 Impact factor: 1.779