Relationship among VEGF, VEGF receptor, AGEs, and macrophages in proliferative diabetic retinopathy

Kakehashi, Akihiro; Inoda, Satoru; Mameuda, C.; Kuroki, Masahide; Jono, Tadashi; Nagai, Ryo; Horiuchi, Seikoh; Kawakami, Masanobu; Kanazawa, Yasunori

doi:10.1016/j.diabres.2007.10.018

Cited by 45 publications

(25 citation statements)

References 26 publications

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“…However, the mean aqueous humor VEGF level in neovascular AMD or PCV tended to be higher than that in controls, it might be because of small sample size in the present study. Many studies have demonstrated that aqueous humor VEGF levels are higher in proliferative diabetic retinopathy or central retinal vein occlusion compared with controls [24,25,26,27]. Distinct from panretinal disorders, such as proliferative diabetic retinopathy or central retinal vein occlusion, neovascular AMD or PCV is a focal macular disease, which may be the reason why aqueous VEGF levels in these eyes were not significantly different from those in controls in the present study.…”

Section: Discussionsupporting

confidence: 46%

Aqueous Humor Cytokine Levels in Patients with Polypoidal Choroidal Vasculopathy and Neovascular Age-Related Macular Degeneration

Sakurada

Nakamura²,

Yoneyama³

et al. 2014

Ophthalmic Res

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Purpose: To investigate the possible roles of various cytokines or growth factors in the pathogenesis of exudative age-related macular degeneration (AMD) by comparing aqueous humor levels of 14 cytokines between eyes with polypoidal choroidal vasculopathy (PCV) and those with neovascular AMD. Methods: Forty eyes from 40 patients with treatment-naïve exudative AMD consisting of 18 eyes with neovascular AMD and 22 eyes with PCV were studied. Twenty eyes from 20 patients with no retinal pathology who underwent cataract surgery served as controls. Aqueous humor samples were collected just before intravitreal ranibizumab injection in 40 eyes with exudative AMD and before cataract surgery in 20 control eyes. Concentrations of 14 cytokines were determined by chemiluminescence-based ELISA: interleukin (IL)-1α, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, IL-15, IL-17, vascular endothelial growth factor (VEGF), monocyte chemoattractant protein 1, interferon-γ-inducible protein (IP)-10 and C-reactive protein (CRP). Results: After adjusting for gender, age and axial length, concentrations of CRP and IP-10 were significantly higher in eyes with neovascular AMD or PCV compared with control eyes (p < 0.05), and IP-10 levels were strongly associated with lesion size (p = 0.002). None of the 14 cytokines, including VEGF, were significantly different between eyes with neovascular AMD and those with PCV. Conclusion: Aqueous humor concentrations of CRP and IP-10 were elevated in eyes with PCV or neovascular AMD. IP-10 could be associated with the pathogenesis of neovascular AMD and PCV. © 2014 S. Karger AG, Basel

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Section: Discussionsupporting

confidence: 46%

Aqueous Humor Cytokine Levels in Patients with Polypoidal Choroidal Vasculopathy and Neovascular Age-Related Macular Degeneration

Sakurada

Nakamura²,

Yoneyama³

et al. 2014

Ophthalmic Res

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“…One major drawback of its use is the high rate of complications, such as cataract formation and marked elevation of IOP [18]. Supported by a number of experimental studies [19,20,21,22,23,24], VEGF inhibitors have been introduced for the treatment of various retinal vascular diseases. Bevacizumab is a humanized monoclonal antibody that binds to all subforms of VEGF [25].…”

Section: Discussionmentioning

confidence: 99%

Comparison of Intravitreal Bevacizumab versus Triamcinolone for the Treatment of Diffuse Diabetic Macular Edema

et al. 2010

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Background: Our purpose was to compare the effect of triamcinolone and bevacizumab (Avastin) on the retinal thickness and functional outcome in patients with diabetic macular edema. Methods and Materials: A collective of 32 patients, who had been treated by a single 4.0-mg intravitreal triamcinolone injection (group 1), was matched to 32 patients (‘matched pairs’), who had received 3 injections of 1.25 mg of bevacizumab within 3 months in 4-week intervals (group 2). The outcome variables were changes in best corrected visual acuity (VA) and central retinal thickness 3 months after therapy. Results: Both groups did not differ regarding preoperative VA and central retinal thickness measured by optical coherence tomography. The baseline mean VA was 0.72 ± 0.39 logMAR in group 1 and 0.73 ± 0.39 logMAR in group 2 (p = 0.709). The mean central retinal thickness measured by optical coherence tomography was 548 ± 185 µm in group 1 and 507 ± 192 µm in group 2. While the patients in group 1 experienced a slight increase in VA of on average 0.7 lines following a single triamcinolone injection to a mean of 0.64 ± 0.40 logMAR (p = 0.066) after 3 months, the patients in group 2 showed almost no effect on VA with an average increase of 0.2 lines to a mean VA of 0.72 ± 0.30 logMAR (p = 0.948) following 3 intravitreal injections of bevacizumab. Comparing the effect on VA between both groups no statistically significant difference (p = 0.115) was noted. Concerning decrease in central retinal thickness both therapies were highly effective (p < 0.001 each), again, without statistically significant difference between the groups (p < 0.128). Conclusion: Our data suggest that a single triamcinolone injection may be as effective as a 3 times repeated intravitreal administration of bevacizumab for the treatment of diabetic macular edema. Further prospective trials should be performed.

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“…While our current studies were not designed to characterize the pattern-recognition receptor(s) involved in the response, the polarized nature of the response would argue that the receptor for AGE, RAGE, was on the apical side of the cells and is affected by any AGE increase in the vitreous (Yokoi et al, 2005;Yamagishi et al, 2006;Kakehashi et al, 2008). Increase in intravitreal AGEs (which can originate from leakage of blood through the inner retina vessels, or can be generated in the retina in situ) would then in turn disrupt RPE-barrier function, causing further increase in AGE accumulation in the ocular environment.…”

Section: Discussionmentioning

confidence: 99%

“…Diabetic retinopathy is a major complication of diabetes mellitus and a leading cause of visual impairment and blindness in the United States (Aiello, 2003). The progression of diabetic retinopathy is associated with the accumulation of AGE in the retina and vitreous (Yokoi et al, 2005;Yamagishi et al, 2006;Kakehashi et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

C-Type Natriuretic Peptide Protects the Retinal Pigment Epithelium against Advanced Glycation End Product–Induced Barrier Dysfunction

Dahrouj

Alsarraf

Liu

et al. 2012

J Pharmacol Exp Ther

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In diabetic retinopathy, vision loss is usually secondary to macular edema, which is thought to depend on the functional integrity of the blood-retina barrier. The levels of advanced glycation end products in the vitreous correlate with the progression of diabetic retinopathy. Natriuretic peptides (NP) are expressed in the eye and their receptors are present in the retinal pigment epithelium (RPE). Here, we investigated the effect of glycated-albumin (Glyc-alb), an advanced glycation end product model, on RPE-barrier function and the ability of NP to suppress this response. Transepithelial electrical resistance (TEER) measurements were used to assess the barrier function of ARPE-19 and human fetal RPE (hfRPE) monolayers. The monolayers were treated with 0

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Relationship among VEGF, VEGF receptor, AGEs, and macrophages in proliferative diabetic retinopathy

Cited by 45 publications

References 26 publications

Aqueous Humor Cytokine Levels in Patients with Polypoidal Choroidal Vasculopathy and Neovascular Age-Related Macular Degeneration

Aqueous Humor Cytokine Levels in Patients with Polypoidal Choroidal Vasculopathy and Neovascular Age-Related Macular Degeneration

Comparison of Intravitreal Bevacizumab versus Triamcinolone for the Treatment of Diffuse Diabetic Macular Edema

C-Type Natriuretic Peptide Protects the Retinal Pigment Epithelium against Advanced Glycation End Product–Induced Barrier Dysfunction

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