Ocular vascular endothelial growth factor levels in diabetic rats are elevated before observable retinal proliferative changes

Sone, Hirohito; Kawakami, Yasushi; Okuda, Yukichi; Sekine, Yasuo; Honmura, Sachiko; Matsuo, Katsuhiko; Segawa, Toshiaki; Suzuki, Hideo; Yamashita, Kamejiro

doi:10.1007/s001250050740

Cited by 122 publications

(66 citation statements)

References 11 publications

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“…Increased levels of VEGF have also been detected in the eyes of diabetic animals [19][20][21]. In our immunohistochemical study we also showed increased immunoreactivity of VEGF in the SDT-NRS and SDT-PR rats, with the difference between these two groups being the intensity of immunoreactivity and location of staining in the vascular endothelial cells.…”

Section: Discussionsupporting

confidence: 76%

Retinal neovascularisation without ischaemia in the spontaneously diabetic Torii rat

Yamada

Higuchi

et al. 2005

Diabetologia

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Aims/hypothesis: The spontaneously diabetic Torii (SDT) rat has recently been established as a model of type 2 human diabetes mellitus. Male SDT rats develop severe diabetic ocular complications. This study investigated the nature of the ocular complications in this model and addressed the question of whether the SDT rat is a good model of human proliferative diabetic retinopathy. Methods: Male SDT rats aged 50 weeks were studied for a period of 8 months. Under deep anaesthesia, one eye of each animal was enucleated following perfusion with fluorescein dextran and a retinal flat mount was prepared to study vascular structure. The other eye was enucleated and investigated histologically by haematoxylin-eosin and azan staining and by immunohistochemistry using antibodies against vascular endothelium (Griffonia simplicifolia isolectin B4 antibody) and vascular endothelial growth factor (VEGF). Results: From the vascular structure study, 17 of 32 rats (53%) showed proliferative retinopathy without vascular non-perfusion. The histological study revealed traction retinal folds in rats with proliferative retinopathy. Azan staining showed some proliferative matrix in rats with normal retinal structure and those with proliferative retinopathy compared with normoglycaemic controls. Staining with Griffonia simplicifolia isolectin B4 antibody showed no specific vascular changes in any of the rats, while VEGF staining revealed higher immunoreactivity in the retina of rats with normal retinal structure and those with proliferative retinopathy, but only low immunoreactivity in the control animals. Conclusions/ interpretation: There appear to be differences between the SDT rat model of diabetic retinopathy and human proliferative diabetic retinopathy, as the SDT rat develops retinal neovascularisation without retinal ischaemia. This very unique display of ocular neovascularisation may be caused by increased expression of VEGF.

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Section: Discussionsupporting

confidence: 76%

Retinal neovascularisation without ischaemia in the spontaneously diabetic Torii rat

Yamada

Higuchi

et al. 2005

Diabetologia

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“…in the absence of neovascularisation [30][31][32][33][34][35]. Interestingly, other formulations of α-lipoic acid, given for shorter periods, produced complete inhibition of VEGF in the diabetic retina [10].…”

Section: Discussionmentioning

confidence: 99%

Effect of R-(+)-α-lipoic acid on experimental diabetic retinopathy

et al. 2006

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Aims/hypothesis: Hyperglycaemia-induced mitochondrial overproduction of reactive oxygen species (ROS) is central to the pathogenesis of endothelial damage in diabetes. R-(+)-α-lipoic acid has advantages over classic antioxidants, as it distributes to the mitochondria, is regenerated by glycolytic flux, and has a low redox potential. Methods: To assess the effect of R-(+)-α-lipoic acid on experimental diabetic retinopathy, three groups of male Wistar rats were studied: nondiabetic controls, untreated diabetic controls, and diabetic rats treated with 60 mg/kg bodyweight R-(+)-α-lipoic acid i.p. for 30 weeks. Quantitative retinal morphometry included acellular occluded capillaries and pericyte numbers. The effects of R-(+)-α-lipoic acid on parameters of oxidative and nitrative stress, AGE and its receptor and nuclear factor kappa B (NFκB) were assessed by immunoblotting, and NFκB activation by electrophoretic mobility shift assay. Angiopoietin-2 and vascular endothelial growth factors were also determined by immunoblotting. Results: After 30 weeks of diabetes, the number of acellular capillaries was significantly elevated in diabetic rats (57.1±10.6 acellular capillary segments [ac]/mm 2 of retinal area) compared with nondiabetic (19.8±5

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“…Although diabetes in the rodent model is not associated with proliferative retinopathy it does develop increased retinal vascular permeability [27,48,49] in association with increased retinal VEGF expression [21,50]. In adult primates intravitreal injections of VEGF leads to many of the changes associated with non-proliferative diabetic including oedema, microaneurysms and intraretinal haemorrhages [51] suggesting that VEGF has a key role in non-proliferative as well as proliferative retinopathy.…”

Section: Discussionmentioning

confidence: 99%

Angiotensin converting enzyme inhibition reduces retinal overexpression of vascular endothelial growth factor and hyperpermeability in experimental diabetes

et al. 2000

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Despite laser photocoagulation therapy, diabetic retinopathy remains a common cause of visual impairment and blindness [1], principally as a consequence of proliferative retinopathy and macular oedema. Although the pathogenesis of these retinal disorders characterized by retinal neovascularization and exudation is incompletely understood, recent evidence has implicated the vascular endothelial growth factor (VEGF), a permeability-inducing and endothelial cell selective angiogenic glycoprotein as a key factor [2±4].Although plasma renin is suppressed in diabetes, experimental evidence suggests that the tissue reninangiotensin system (RAS) is activated in the setting of chronic hyperglycaemia [5] and that its blockade underlies the beneficial effects of angiotensin converting enzyme (ACE) inhibition in diabetic nephropathy [6] and cardiovascular disease [7]. Previous

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Ocular vascular endothelial growth factor levels in diabetic rats are elevated before observable retinal proliferative changes

Cited by 122 publications

References 11 publications

Retinal neovascularisation without ischaemia in the spontaneously diabetic Torii rat

Retinal neovascularisation without ischaemia in the spontaneously diabetic Torii rat

Effect of R-(+)-α-lipoic acid on experimental diabetic retinopathy

Angiotensin converting enzyme inhibition reduces retinal overexpression of vascular endothelial growth factor and hyperpermeability in experimental diabetes

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