Control of chemokine production at the blood–retina barrier

Abstract

SUMMARYChemokine production at the blood±retina barrier probably plays a critical role in determining the in¯ux of tissue-damaging cells from the circulation into the retina during in¯ammation. The blood± retina barrier comprises the retinal microvascular endothelium and the retinal pigment epithelium. Chemokine expression and production by human retinal microvascular endothelial cells (REC) have never been reported previously, so we examined the in vitro expression and production of monocyte chemoattractant protein-1 (MCP-1), regulated on activation of normal T-cell expressed and secreted (RANTES), macrophage in¯ammatory protein (MIP)-1a, MIP-1b, interleukin (IL)-8, epithelial cell-derived neutrophil activating protein-78 (ENA-78) and growth related oncogene a (GROa) in these cells, both unstimulated and stimulated by cytokines likely to be present during the evolution of an in¯ammatory response. We compared this to expression and production of these chemokines in vitro in human retinal pigment epithelial cells (RPE). MCP-1 was expressed and produced constitutively by REC but all the chemokines were produced in greater amounts upon stimulation with the proin¯ammatory cytokines IL-1b and tumour necrosis factor-a (TNF-a). MCP-1 and IL-8 were produced at much higher levels than the other chemokines tested. MIP-1a and MIP-1b were present only at low levels, even after stimulation with IL-1b and TNF-a. Cytokines with greater anti-in¯ammatory activity, such as IL-4, IL-10, IL-13, transforming growth factor-b (TGF-b) and IL-6, had little effect on chemokine production either by REC alone or after stimulation with IL-1b and TNF-a. RPE, although a very different cell type, showed a similar pattern of expression and production of chemokines, indicating the site-speci®c nature of chemokine production. Chemokine production by REC and RPE is probably signi®cant in selective leucocyte recruitment during the development of in¯ammation in the retina.

Prevalence and risk factors of diabetic retinopathy in Chongqing pre-diabetes patients

“…The cytokines and mediators are said to contribute actively to DR-associated damage to the retinal vasculature and neovascularization. 23 RANTES produced by inflammatory cells, retinal endothelial cells, and pigment epithelial cells 24 is a member of the chemokine family. Meleth et al 7 showed that RANTES levels largely increased in subjects with severe NPDR versus less severe NPDR (Po0.001), but RANTES levels unexpectedly decreased in subjects with less severe NPDR versus normal controls.…”

An apolipoprotein E variant may protect against age‐related macular degeneration through cytokine regulation

“…These findings implicate a possible mechanism underlying the observed protective effect of this allele. RPE cells constitutively express CCL2, a CC chemokine, and secrete VEGF, a growth factor and cytokine [Holtkamp et al, 1999;Crane et al, 2000]. Increased levels of both CCL2 and VEGF in RPE cells are related to oxidative stress and hypoxia within the eye [Spilsbury et al, 2000;Uetama et al, 2003].…”

Vitreous levels of interleukine-8 and monocyte chemoattractant protein-1 in macular oedema with branch retinal vein occlusion

“…In vitro expression and production of IL-8 and MCP-1 by human retinal endothelial cells and HRPE after stimulation by pro-inflammatory cytokines have been reported. 10 MCP-1 significantly reduced ZO-1 protein expression in a mouse model of experimental autoimmune uveoretinitis. 24 Recently, Funk et al 25 reported elevated aqueous humour levels of IL-8 and MCP-1 in patients with CRVO, but not in those with BRVO.…”

“…[7][8][9] Moreover, both IL-8 and MCP-1 are expressed by human retinal endothelial cells and retinal pigment epithelial cells (HRPE). 10 In this study, we measured the concentrations of IL-8 and MCP-1 in vitreous fluid of patients with macular oedema secondary to BRVO to investigate the relationship between the development of macular oedema and the vitreous levels of these chemokines.…”