A model system for the study of human retinal angiogenesis: activation of monocytes and endothelial cells and the association with the expression of the monocarboxylate transporter type 1 (MCT-1)

Knott, Rachel M.; Robertson, Marcus; Muckersie, Elizabeth; Folefac, V. A.; Fairhurst, F. E.; Wileman, Samantha; Forrester, John V.

doi:10.1007/s001250051240

Cited by 28 publications

(26 citation statements)

References 30 publications

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“…These exogenous cells may be the main source of both VGEF and VCAM-1 within the ischemic retina. Certainly, macrophages and lymphocytes have been identified in epiretinal membranes from patients with PDR (31-33), and activated macrophages have been detected in a model of human retinal angiogenesis (34). Altogether, these observations support the concept that cellular adhesion and angiogenesis may be linked processes.…”

Section: Vcam-1 and Vegf In Diabetic Retinopathymentioning

confidence: 76%

Vitreous Levels of Vascular Cell Adhesion Molecule and Vascular Endothelial Growth Factor in Patients With Proliferative Diabetic Retinopathy

Hernández¹,

Burgos²,

Cantón³

et al. 2001

Diabetes Care

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OBJECTIVE -To evaluate the intravitreous concentration of vascular cell adhesion molecule (VCAM)-1 in diabetic patients with proliferative diabetic retinopathy (PDR) and the relationship of VCAM-1 with vascular endothelial growth factor (VEGF).RESEARCH DESIGN AND METHODS -Serum and vitreous fluid samples were obtained simultaneously at the onset of vitrectomy from 20 diabetic patients with PDR and 20 nondiabetic control subjects with nonproliferative ocular disease. Both groups were matched by serum levels of VCAM-1 and VEGF. VCAM-1 and VEGF were determined by enzyme-linked immunosorbent assay. Statistics were determined using the Mann-Whitney U test and Spearman's rank correlation test.RESULTS -The intravitreous concentration of VCAM-1 was significantly elevated in diabetic patients with PDR compared with control subjects (26 ng/ml [19 -118] vs. 22 ng/ml [20 -47], P Ͻ 0.05). A direct correlation between VCAM-1 and total vitreous proteins was detected in diabetic patients (r ϭ 0.64, P ϭ 0.003), but not in control subjects. After adjusting for total intravitreous proteins, VCAM-1 was significantly lower in diabetic patients with PDR than in control subjects (8.2 ng/ml [4 -31.4] vs. 43.1 ng/ml [9.7-100], P Ͻ 0.001). Intravitreous VEGF concentrations were higher in patients with PDR than in control subjects in absolute terms (1.34 ng/ml [0.16 -6.22] vs. 0.009 ng/ml [0.009 -0.044], P Ͻ 0.0001) and after correcting for total vitreal proteins (0.33 ng/ml [0.01-2.3] vs. 0.013 ng/ml [0.003-0.035], P ϭ 0.0001). Finally, the vitreous ratio of VCAM-1 to proteins correlated with the vitreous ratio of VEGF to proteins in both diabetic patients (r ϭ 0.74, P ϭ 0.001) and control subjects (r ϭ 0.84, P ϭ 0.005).CONCLUSIONS -The low proportion of VCAM-1 in relation to total vitreal proteins observed in diabetic patients with PDR suggests that VCAM-1 is quenched by diabetic retina. In addition, the direct correlation detected between VCAM-1 and VEGF suggests that cellular adhesion and neovascularization may be linked processes. Diabetes Care 24:516 -521, 2001P roliferative diabetic retinopathy (PDR) is characterized by extensive neovascularization and vessel intrusion into the vitreous body, with subsequent bleeding and scarring surrounding new vessels, leading to severe visual impairment. Ischemic areas of the retina seem to be essential stimuli for the angiogenic process mediated by specific growth factors. This includes the expression of vascular endothelial growth factor (VEGF) by retinal glial cells (1) and vascular endothelial cells (2). It is thought that capillary occlusion by increased adhesion of leukocytes and macrophages to the endothelium has a crucial role in the process of retinal ischemia (3). In addition, monocytes exposed to glycated collagen show increased adhesiveness (4), and several studies indicate that circulating leukocytes are activated in diabetic patients (5,6).Vascular cell adhesion molecule (VCAM)-1, a member of the immunoglobulin supergene family of cellular adhesion molecules, is involved in the re...

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Section: Vcam-1 and Vegf In Diabetic Retinopathymentioning

confidence: 76%

Vitreous Levels of Vascular Cell Adhesion Molecule and Vascular Endothelial Growth Factor in Patients With Proliferative Diabetic Retinopathy

Hernández¹,

Burgos²,

Cantón³

et al. 2001

Diabetes Care

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“…Secondary sprouting may also be measured after the original tubules collapse (Castellon et al, 2002). To recognize the impact of the microenvironment on endothelial cell behavior, and the potential for dedifferentiation of endothelial cells in culture, other groups have described technically challenging assays, in which outgrowth of vessels from retinal explants is measured (Im et al, 2005; Knott et al, 1999)…”

Section: Retinal Ischemic Vasculopathiesmentioning

confidence: 99%

Role of the retinal vascular endothelial cell in ocular disease

Bharadwaj

Appukuttan

Wilmarth

et al. 2013

Progress in Retinal and Eye Research

136

114

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Retinal endothelial cells line the arborizing microvasculature that supplies and drains the neural retina. The anatomical and physiological characteristics of these endothelial cells are consistent with nutritional requirements and protection of a tissue critical to vision. On the one hand, the endothelium must ensure the supply of oxygen and other nutrients to the metabolically active retina, and allow access to circulating cells that maintain the vasculature or survey the retina for the presence of potential pathogens. On the other hand, the endothelium contributes to the blood-retinal barrier that protects the retina by excluding circulating molecular toxins, microorganisms, and pro-inflammatory leukocytes. Features required to fulfill these functions may also predispose to disease processes, such as retinal vascular leakage and neovascularization, and trafficking of microbes and inflammatory cells. Thus, the retinal endothelial cell is a key participant in retinal ischemic vasculopathies that include diabetic retinopathy and retinopathy of prematurity, and retinal inflammation or infection, as occurs in posterior uveitis. Using gene expression and proteomic profiling, it has been possible to explore the molecular phenotype of the human retinal endothelial cell and contribute to understanding of the pathogenesis of these diseases. In addition to providing support for the involvement of well-characterized endothelial molecules, profiling has the power to identify new players in retinal pathologies. Findings may have implications for the design of new biological therapies. Additional progress in this field is anticipated as other technologies, including epigenetic profiling methods, whole transcriptome shotgun sequencing, and metabolomics, are used to study the human retinal endothelial cell.

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“…Preparation of Retinal Explants-The vessel outgrowth procedure was a modification of a previously published protocol (19,27). Briefly, a collagen gel mixture was prepared as described for the tube formation assay, and 400 l was placed into each well of 24-well plate and incubated at 37°C for 2 h to allow the gel to solidify.…”

Section: Methodsmentioning

confidence: 99%

Src Family Kinases Promote Vessel Stability by Antagonizing the Rho/ROCK Pathway

Kazlauskas

2007

Journal of Biological Chemistry

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Src family kinases (SFKs) are one of the signaling enzymes that contribute to angiogenesis, but their precise input to the various phases of the angiogenic program has not been defined. Using an in vitro model system, we discovered that SFKs promoted the formation of tubes and prevented their regression. They suppressed regression by activating the ERK pathway that antagonized the Rho/ROCK pathway, which was essential for regression. These studies reveal that SFKs contribute to several phases of the angiogenic program and identify the downstream effectors by which SFKs stabilize tubes.

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A model system for the study of human retinal angiogenesis: activation of monocytes and endothelial cells and the association with the expression of the monocarboxylate transporter type 1 (MCT-1)

Cited by 28 publications

References 30 publications

Vitreous Levels of Vascular Cell Adhesion Molecule and Vascular Endothelial Growth Factor in Patients With Proliferative Diabetic Retinopathy

Vitreous Levels of Vascular Cell Adhesion Molecule and Vascular Endothelial Growth Factor in Patients With Proliferative Diabetic Retinopathy

Role of the retinal vascular endothelial cell in ocular disease

Src Family Kinases Promote Vessel Stability by Antagonizing the Rho/ROCK Pathway

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