Silver nanoparticles inhibit VEGF-and IL-1β-induced vascular permeability via Src dependent pathway in porcine retinal endothelial cells

Vascular endothelial barrier dysfunction occurs in a large number of disease processes including diabetic retinopathy, stroke, pulmonary edema, myocardial infarction, inflammatory bowel disease, nephropathies, rheumatoid arthritis, and tumours. In these diseases, increased vascular permeability is associated with elevated levels of either one or more growth factors or cytokines [1]. Vascular endothelial growth factor (VEGF) has received considerable attention as a tumour-secreted vascular permeability factor [2,3]. VEGF is determined to posses 50,000 times more potency than histamine in inducing vasopermeability in the dermal vasculature. Previous reports indicate the correlation between the increases in permeability in ischemic retinopathies and possibly also in exudative macular degeneration and uveitis and the increased VEGF levels [4-7]. In fact, VEGF antagonists have been successfully used to reduce retinal/macular edema in neovascular eye diseases such as age-related macular degeneration with stabilization or even improvement of visual acuity in a subset of affected patients [8]. Although VEGF is thought to play a major role in stimulating vascular permeability, this process undoubtedly involves multiple other factors as well, including inflammatory cytokines such as interleukin-1beta (IL-1β) [9]. Previously IL-1β was shown to induce the permeability through the vasculature of the blood retinal barrier in rats [10].Now a great deal of research is focused on the development of inhibitors for vascular permeability. In fields like drug delivery, imaging and diagnosis & treatment of cancer various nanoparticles are proposed to function as a tool [11,12]. Furthermore, currently efforts are being made to investigate the use of nanomaterials in various therapeutic applications, where the nanoparticles could be the active component or could just be the physical support for the functional moieties. In addition, the importance of augmenting the performance of convention