Vitreous Levels of Placenta Growth Factor and Vascular Endothelial Growth Factor in Patients With Proliferative Diabetic Retinopathy

Mitamura, Yoshinori; Tashimo, Asako; Nakamura, Yasushi; Tagawa, Hiroshi; Ohtsuka, Kenji; Mizue, Yuka; Nishihira, Jun

doi:10.2337/diacare.25.12.2352

Cited by 78 publications

(59 citation statements)

References 7 publications

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“…VEGF levels in our study ranged from 0.13 ng/ml to Ͼ12.0 ng/ml (shown as pg/ml in Fig. 6) after intravitreal injection of AAV.VEGF and were thus highly comparable with those noted in humans with proliferative retinopathy, reported to range between 0.065, 1.28, and 168,000 ng/ml (22)(23)(24)(25)(26)(27).…”

Section: Discussionsupporting

confidence: 84%

“…This suggests that VEGF produced after subretinal injection does not readily diffuse across the multilayered retina either because it is too large or because it becomes bound to receptors that are abundant in the outer retina. Interestingly, significantly elevated VEGF protein levels are found in intraocular fluid samples from individuals with inner (but not outer) retinal neovascularization (22)(23)(24)(25)(26)(27).…”

Section: Discussionmentioning

confidence: 99%

“…High levels of VEGF are present in anterior chamber, vitreous, and tissue samples from humans with diabetic retinopathy, choroidal neovascularization (CNV), and neovascular glaucoma compared with healthy individuals (21)(22)(23)(24)(25)(26)(27). Delivery of VEGF protein was therefore a logical approach with which to generate an animal model of retinal neovascularization.…”

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confidence: 99%

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Nonhuman Primate Models for Diabetic Ocular Neovascularization Using AAV2-Mediated Overexpression of Vascular Endothelial Growth Factor

et al. 2005

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Neovascularization leads to blindness in numerous ocular diseases, including diabetic retinopathy, agerelated macular degeneration, retinopathy of prematurity, and sickle cell disease. More effective and stable treatments for ocular neovascularization are needed, yet there are major limitations in the present animal models. To develop primate models of diabetic retinopathy and choroidal neovascularization, rhesus monkeys were injected subretinally or intravitreally with an adeno-associated virus (AAV)-2 vector carrying the cDNA encoding human vascular endothelial growth factor (VEGF). Overexpression of VEGF was measured by intraocular fluid sampling over time. Neovascularization was evaluated by ophthalmoscopy through angiography, optical coherence tomography, and ultimately histopathology. Overexpression of VEGF through AAV2 results in rapid development of features of diabetic retinopathy or macular edema, depending on the targeted cell type/mode of production of VEGF and diffusion of VEGF. Nonhuman primate models will be useful in testing long-term safety and efficacy of novel therapeutic agents for blinding neovascular diseases. Diabetes 54:1141-1149, 2005 D iabetic retinopathy is the most common microvascular complication of diabetes, resulting in blindness for Ͼ10,000 people with diabetes per year. Chronic diabetes can also result in macular edema, neovascular glaucoma, and neovascularization of the optic disc. There are other conditions in which such pathology can develop, including retinopathy of prematurity, sickle cell retinopathy, and retinal vein occlusion.Diabetic ocular neovascularization and related conditions are leading causes of blindness around the world.Current treatment options for retinal neovascularization are limited to interventional (1-3) or surgical (4,5) procedures. These treatments are often suboptimal, as they are only suitable for a subset of patients, may stabilize vision loss for only a limited time, and can, themselves, destroy functioning retina. In addition, recurrence of neovascularization is frequent.Therefore, a number of experimental antiangiogenic therapies have evolved over the last couple of years (rev. in 6). Their aim is to inhibit vessel growth by blocking angiogenic factors like vascular endothelial growth factor (VEGF) using antibodies (7,8), interference RNA (9), or chimeric or soluble VEGF receptor proteins (10,11). Alternatively, they try to induce antiangiogenic activity using enzyme inhibitors (12), fungus-derived antiangiogenic agents (13), or viral vector-mediated delivery of a range of compounds including pigment epithelium-derived factor (14,15), tissue inhibitor of metalloproteinases-3, endostatin, or angiostatin (16).Even though some of these experimental therapies have been moved to human clinical trials already, the lack of large animal models for ocular neovascularization prevents thorough testing of these substances beforehand. In addition, the paucity of available rodent animal models makes it difficult to select the most appropriate targets for anti...

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Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Nonhuman Primate Models for Diabetic Ocular Neovascularization Using AAV2-Mediated Overexpression of Vascular Endothelial Growth Factor

et al. 2005

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“…These two common diabetes complications exhibit a very different behavior in terms of angiogenic response to ischemia, and this contrast has been termed "diabetic paradox." Many growth factors have been proposed to have a role in this phenomenon (13)(14)(15), all of which are potent stimuli for progenitor cell mobilization and homing to ischemic tissues (16). Indeed, recent data indicate that marrow-derived cells are involved in retinal neovascularization and that DR ϩ patients have increased levels of circulating progenitors (8,17).…”

Section: Conclusion -We Show That Cd34 ϩ Cells and Cd34mentioning

confidence: 99%

Endothelial Progenitor Cells and the Diabetic Paradox

et al. 2006

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“…A number of studies have identified factors associated with the pathogenesis of PDR, e.g., angiogenic factors like vascular endothelial growth factor [9][10][11][12], angiotensin-converting enzyme [13], insulin-like growth factor (IGF) [14], angiopoietin [15], erythropoietin [16], placenta growth factor [17], and advanced glycation end product [18], and antiangiogenic factors like pigment epithelium-derived factor (PEDF) [19][20][21]. However, the majority of previous studies have focused on sets of targeted proteins, particularly on the molecules involved in angiogenesis and cellular proliferation, which makes it difficult to evaluate changes in entire vitreous humor protein profiles and to identify novel markers of PDR pathogenesis.…”

Section: Introductionmentioning

confidence: 99%

Profiling of vitreous proteomes from proliferative diabetic retinopathy and nondiabetic patients

Kim

et al. 2007

Proteomics

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Diabetes can lead to serious microvascular complications like proliferative diabetic retinopathy (PDR), which is the leading cause of blindness in adults. The proteomic changes that occur during PDR cannot be measured in the human retina for ethical reasons, but could be reflected by proteomic changes in vitreous humor. Thus, we considered that comparisons between the proteome profiles of the vitreous humors of PDR and nondiabetic controls could lead to the discovery of novel pathogenic proteins and clinical biomarkers. In this study, the authors used several proteomic methods to comprehensively examine vitreous humor proteomes of PDR patients and nondiabetic controls. These methods included immunoaffinity subtraction (IS)/2-DE/ MALDI-MS, nano-LC-MALDI-MS/MS, and nano-LC-ESI-MS/MS. The identified proteins were subjected to the Trans-Proteomic Pipeline validation process. Resultantly, 531 proteins were identified, i.e., 415 and 346 proteins were identified in PDR and nondiabetic control vitreous humor samples, respectively, and of these 531 proteins, 240 were identified for the first time in this study. The PDR vitreous proteome was also found to contain many proteins possibly involved in the pathogenesis of PDR. The proteins described provide the most comprehensive proteome listing in the vitreous humor samples of PDR and nondiabetic control patients.

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Vitreous Levels of Placenta Growth Factor and Vascular Endothelial Growth Factor in Patients With Proliferative Diabetic Retinopathy

Cited by 78 publications

References 7 publications

Nonhuman Primate Models for Diabetic Ocular Neovascularization Using AAV2-Mediated Overexpression of Vascular Endothelial Growth Factor

Nonhuman Primate Models for Diabetic Ocular Neovascularization Using AAV2-Mediated Overexpression of Vascular Endothelial Growth Factor

Endothelial Progenitor Cells and the Diabetic Paradox

Profiling of vitreous proteomes from proliferative diabetic retinopathy and nondiabetic patients

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