Abstract：
:Diabetic retinopathy (DR) is a secondary complication of diabetes. DR can cause irreversible blindness, and its pathogenesis is considered multifactorial. DR can progress from non-proliferative DR to proliferative DR, characterized by retinal neovascularization. The main cause of vision loss in diabetic patients is diabetic macular edema, caused by vessel leakage and blood retinal barrier breakdown. Currently, aflibercept is an anti-VEGF approved for diabetic macular edema. Aflibercept can bind several members of vascular permeability factors, namely VEGF-A, B, and PlGF. We analyzed the aflibercept-PlGF complex at molecular level, through an in silico approach. In order to explore the role of PlGF in DR, we treated primary human retinal endothelial cells (HRECs) and mouse retinal epithelial cells (RPEs) with aflibercept and an anti-PlGF antibody. We explored the hypothesis that aflibercept has anti-inflammatory action through blocking of PlGF signaling and the ERK axis in an in vitro and in vivo model of DR. Both aflibercept and the anti-PlGF antibody exerted protective effects on retinal cells, by inhibition of the ERK pathway. Moreover, aflibercept significantly decreased (p < 0.05) the expression of TNF-α in an in vitro and in vivo model of DR. Therefore, our data suggest that inhibition of PlGF signaling, or a selective blocking, may be useful in the management of early phases of DR when the inflammatory process is largely involved.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Lazzara F,Fidilio A,Platania CBM,Giurdanella G,Salomone S,Leggio GM,Tarallo V,Cicatiello V,De Falco S,Eandi CM,Drago F,Bucolo Cdoi
10.1016/j.bcp.2019.07.021subject
Has Abstractpub_date
2019-10-01 00:00:00pages
341-351eissn
0006-2952issn
1873-2968pii
S0006-2952(19)30276-Xjournal_volume
168pub_type
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