Program

PO2-9-13

Adiponectin is a pathological factor for intraocular angiogenesis

[Speaker] Shinsuke Nakamura:1
[Co-author] Tomomi Masuda:1, Shuuji Sakurai:1, Hideaki Kawakami:2, Shinsuke Suemori:3, Kiyofumi Mochizuki:4, Masamitsu Shimazawa:1, Hideaki Hara:1
1:Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Japan, 2:Department of Ophthalmology, Gifu Municipal Hospital, Japan, 3:Department of Ophthalmology, Matsunami General Hospital, Japan, 4:Department of Ophthalmology, Gifu University School of Medicine, Japan

Background
The progression of diabetic retinopathy (DR), is closely associated with pathological retinal angiogenesis, mainly induced by vascular endothelial growth factor (VEGF). Although anti-VEGF therapies are effective in treating ocular neovascularization, they not only show a transient efficacy but also have no effects. New therapeutic target molecules are needed to resolve these issues. According to previous report, adiponectin promoted angiogenesis in vitro and serum and Aqueous humor adiponectin level in type 2 DM patients with DR is higher than those in type 2 DM patients without DR, and adiponectin level is positively correlated with DR severity. On the other hand, molecular mechanisms of ocular angiogenesis are still unknown. So, we studied to determine the relationship between adiponectin and diabetic retinopathy characterized by retinal neovascularization.
Methods
The concentrations of adiponectin and vascular endothelial growth factor (VEGF) in vitreous humor samples with either a macular hole (MH) or proliferative diabetic retinopathy (PDR) with or without intravitreal injection of bevacizumab (IVB) were measured by enzyme-linked immunosorbent assay (ELISA). Then, the effect of adiponectin and AdipoRon (adiponectin receptor agonist) against VEGF-induced cell migration in human retinal microvascular endothelial cells (HRMECs) in culture was investigated. In addition, we studied the effect of adiponectin for MAPK/ERK pathway.
Results
The concentrations of adiponectin and VEGF were significantly higher in the vitreous humor of patients with PDR than in patients with a MH. Then, In vitro assays showed that adiponectin accelerated the VEGF-induced cell migration, but not normal cell migration. This promotive effect of adiponectin against VEGF-induced cell migration was suppressed by knockdown adiponectin receptor (AdipoR) 1 and/or AdipoR2. Moreover, adiponectin phosphorylated extracellular signal-regulated kinase (ERK) 1/2 in HRMECs.
Conclusion
These results demonstrated that adiponectin has a proangiogenic effect through AdipoR1 and/or AdipoR2 signaling, suggesting that adiponectin is involved in the pathogenesis of diabetic retinopathy characterized by retinal angiogenesis via ERK1/2.
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