Upregulation of VEGF in Murine Retina via Monocyte Recruitment after Retinal Scatter Laser Photocoagulation

Itaya, M.; Sakurai, Eiji; Nozaki, Miho; Yamada, Kiyoshi; Yamasaki, Satoshi; Asai, Kiyofumi; Ogura, Yuichiro

doi:10.1167/iovs.07-0156

Cited by 69 publications

(62 citation statements)

References 30 publications

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“…Furthermore, several studies have suggested that the expression of various chemokines can be regulated by complement activation products, including MAC (39 -42). It is also known that various chemokines can modulate the levels of growth factors (43)(44)(45)(46). However, the link between MAC, chemokines, and growth factors in laser-induced CNV is not elucidated thus far.…”

Section: Discussionmentioning

confidence: 99%

Relationship between Complement Membrane Attack Complex, Chemokine (C-C Motif) Ligand 2 (CCL2) and Vascular Endothelial Growth Factor in Mouse Model of Laser-induced Choroidal Neovascularization

Liu

Jha

Lyzogubov

et al. 2011

Journal of Biological Chemistry

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The present study investigated the interactions among the complement membrane attack complex (MAC), CCL2, and VEGF that occur in vivo during the development of choroidal neovascularization (CNV). We first investigated the sequential expression of MAC, CCL2, and VEGF during laser-induced CNV in C57BL/6 mice. Increased MAC deposition was detected at 1 h, CCL2 increased at 3 h, and VEGF was up-regulated at day 3 post-laser treatment. These results suggested that during laser-induced CNV, MAC, CCL2 and VEGF are formed and/or expressed in the following order: MAC 3 CCL2 3 VEGF. To determine the cross-talk between MAC, CCL2, and VEGF during laser-induced CNV, neutralizing antibodies were injected both systemically and locally to block the bioactivity of each molecule. Blocking MAC formation inhibited CCL2 and VEGF expression and also limited CNV formation, whereas neutralization of CCL2 bioactivity did not affect MAC deposition; however, it reduced VEGF expression and CNV formation. When bioactivity of VEGF was blocked, CNV formation was significantly inhibited, but MAC deposition was not affected. Together, our results demonstrate that MAC is an upstream mediator and effect of MAC on the development of laser-induced CNV can be attributed to its direct effect on VEGF as well as its effect on VEGF that is mediated by CCL2. Understanding the interplay between immune mediators is critical to gain insight into the pathogenesis of CNV. Age-related macular degeneration (AMD)3 is the major cause of irreversible blindness in individuals over the age of 50 worldwide (1-5). Based on clinical and pathological features, AMD is usually classified into two forms: the nonexudative/dry form and the exudative/wet form (6, 7). Wet AMD is a pathological process, secondary to choroidal neovascular changes (CNV). CNV is a complex pathogenic process where new blood vessels are generated beneath the retina from pre-existing choriocapillaries (8 -10). Several risk factors have been reported to be associated with CNV formation (11-15). Studies reported in the literature support a key role for the complement system in the development of CNV (16 -21).Although the complement system is recognized traditionally as a major component of innate immunity, it has multifunctional role in immunity, including the initiation and regulation of adaptive immune responses (22-26). The role of the complement in the development of CNV has been more directly addressed by using laser-induced animal model (27-29). The laser-induced model of CNV is produced in C57BL/6 mice by laser photocoagulation, and this model is used by an increasing number of investigators (29 -32). Using this animal model of CNV, we demonstrated that complement activation, especially the formation of membrane attack complex (MAC), is crucial for the development of laser-induced CNV (27-29). We also reported that there is a direct correlation between MAC deposition and levels of angiogenic growth factors, including VEGF during laser-induced CNV (29).Studies reported in the literature have indi...

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Section: Discussionmentioning

confidence: 99%

Relationship between Complement Membrane Attack Complex, Chemokine (C-C Motif) Ligand 2 (CCL2) and Vascular Endothelial Growth Factor in Mouse Model of Laser-induced Choroidal Neovascularization

Liu

Jha

Lyzogubov

et al. 2011

Journal of Biological Chemistry

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“…17,19,20,23 The RPE/ choroid complex was carefully isolated from the eyes at 3 days after photocoagulation and sonicated in lysis buffer (20 mM imidazole HCl, 10 mM KCl, 1 mM MgCl 2 , 10 mM EGTA, 1% Triton X-100, 10 mM NaF, 1 mM Na molybdate, 1 mM EDTA, protease inhibitor cocktail [SigmaAldrich, St. Louis, MO]) on ice for 15 minutes. The lysate was centrifuged at 15,000 rpm for 15 minutes at 48C, and the VEGF protein levels in the supernatants were determined using a Quantikine M ELISA kit (threshold of detection, 3 pg/mL; R&D Systems, Minneapolis, MN) that recognizes all splice variants at wavelengths of 450 to 570 nm (SpectraMax340; Molecular Devices, Sunnyvale, CA).…”

Section: Elisa For Vegfmentioning

confidence: 99%

Suppression of Laser-Induced Choroidal Neovascularization by a CCR3 Antagonist

Mizutani¹,

Ashikari²,

Tokoro³

et al. 2013

Invest. Ophthalmol. Vis. Sci.

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“…Laser photocoagulation has been shown to increase the expression of VEGF and transcription factors by cultured human retinal pigment epithelial cells, with upregulation of VEGF occurring from 6 to 72 h [28]. In contrast, Itaya et al [29] reported that the maximum VEGF level was detected on day 3 after photocoagulation in vivo, coinciding with the peak of macrophage infiltration. Furthermore, changes in VEGF mRNA expression were confined to retinal pigment epithelial cells in miniature pigs after laser photocoagulation, with a decrease in expression immediately after photocoagulation and a return to baseline by 42 days [30].…”

Section: Discussionmentioning

confidence: 99%

Vascular Endothelial Growth Factor and Its Soluble Receptors-1 and -2 in Iris Neovascularization and Neovascular Glaucoma

et al. 2014

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Concentrations of vascular endothelial growth factor (VEGF), soluble VEGF receptor-1 (sVEGFR-1) and soluble VEGF receptor-2 (sVEGFR-2) were measured by enzyme-linked immunosorbent assay in 27 proliferative diabetic retinopathy patients who had iris neovascularization (INV) with or without neovascular glaucoma (NVG). The 27 eyes were divided into two groups, consisting of INV without elevation of the intraocular pressure (IOP; INV group) and INV with elevated IOP (NVG group). Ten patients with an idiopathic macular hole were used as the controls. The vitreous levels of VEGF, sVEGFR-1 and sVEGFR-2 showed a significant increase across the three groups. In the INV and NVG groups, the vitreous level of VEGF showed a significant correlation with the levels of sVEGFR-1 and sVEGFR-2. There was also a significant correlation between the vitreous levels of sVEGFR-1 and sVEGFR-2. These results suggest that the vitreous levels of sVEGFR-1 and sVEGFR-2 are dependent on VEGF in patients who have INV with or without NVG.

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Upregulation of VEGF in Murine Retina via Monocyte Recruitment after Retinal Scatter Laser Photocoagulation

Abstract: Retinal scatter laser photocoagulation induced upregulation of VEGF in the sensory retina and RPE-choroid at an early period. The authors speculate that the major source of VEGF in the retina after retinal scatter laser photocoagulation is the recruited monocytes.

Cited by 69 publications

References 30 publications

Relationship between Complement Membrane Attack Complex, Chemokine (C-C Motif) Ligand 2 (CCL2) and Vascular Endothelial Growth Factor in Mouse Model of Laser-induced Choroidal Neovascularization

Relationship between Complement Membrane Attack Complex, Chemokine (C-C Motif) Ligand 2 (CCL2) and Vascular Endothelial Growth Factor in Mouse Model of Laser-induced Choroidal Neovascularization

Suppression of Laser-Induced Choroidal Neovascularization by a CCR3 Antagonist

Vascular Endothelial Growth Factor and Its Soluble Receptors-1 and -2 in Iris Neovascularization and Neovascular Glaucoma

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