Degeneration of Intramural Pericytes in Diabetic Retinopathy

Addison, David J.; Garner, A; Ashton, Norman

doi:10.1136/bmj.1.5691.264

Cited by 85 publications

(31 citation statements)

References 10 publications

(4 reference statements)

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“…DR is the most common microangiopathy in the retina and it is also one of the leading causes of blindness and visual impairment. During proliferative diabetic retinopathy (PDR), the retinal cells go through bi-phasic progression with an initial vaso-obliterative phase and subsequent uncontrolled vaso-proliferative period [27]. In patients with diabetes mellitus, the insulin levels or/and activity is decreased resulting in abnormal glucose metabolism and increased levels of blood glucose.…”

Section: Discussionmentioning

confidence: 99%

“…When total or partial venous outflow occlusion occurs, the retina may develop microaneurysms, hemorrhages, exudates and edema [25,26]. Diabetic retinopathy (DR), is a common complication in patients with diabetes mellitus, most patients with 20 years of diabetes mellitus and with the disease onset before the age of 30, show signs of DR [27]. 50% of DR is proliferative diabetic retinopathy.…”

Section: Discussionmentioning

confidence: 99%

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The Effect of Neovascularization on Human Retinal Pigment Epithelium after Hyperbaric Oxygen Therapy

Chen¹,

Chao²

2017

Health Sci J

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Objective: To investigate the neovascularization effect of hyperbaric oxygen (HBO) therapy on human retinal pigment epithelium (REP) cells. Methods:Human REP cells were cultured in vitro, and divided into normoxic control group and hypoxic control group randomly. The experimental groups were then divided into three subgroups via the different HBO pressure, 0.15 MPa exposed group, 0.2 MPa exposed group, and 0.25 MPa exposed group. The experimental groups were exposed to 100% pure oxygen for 60 and 90 minutes twice, with a 24 hours interval. After HBO exposure the expression of pigment epithelium-derived factor (PEDF) and tumor necrosis factor alpha (TNF-α) by RPE cells were measured by western blot. Results:The western blot result showed that the level of PEDF expression in both experimental groups had an increased trend as the pressure increases with statistical significance (P<0.01). The expression of PEDF in the normoxic group was higher than the hypoxic group. The results showed that the level of TNF-α expression by RPE cells in both experimental groups have a decrease trend as the pressure increases with statistical significance (P<0.01). The results showed that the expression of TNF-α in the hypoxic group was higher when compared to the normoxic group. The duration of HBO exposure has no statistical significance on the level of PEDF and TNF-α expression. Conclusion:This study supports the idea that HBO increases the release of PEDF by RPE cells whither in normoxic and hypoxic conditions, and decreases the release of TNF-α by RPE cells in both conditions, especially in hypoxic state. We also found that HBO can raise the level of PEDF and decrease the level of TNF-α in RPE cells, and has an anti-angiogenic effect which can suppress the formation of neovascularization.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The Effect of Neovascularization on Human Retinal Pigment Epithelium after Hyperbaric Oxygen Therapy

Chen¹,

Chao²

2017

Health Sci J

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“…Nevertheless, the association among hyperglycemia, diabetes, and retinopathy remains to be mechanistically defined (Addison et al, 1970;Harik and LaManna, 1988;Kern and Engerman, 1996;Mann et al, 2003). The primary mechanisms implicated in the pathogenesis of diabetic retinopathy are thought to be biochemical and hemodynamic, all of which are dependent on excessive transport (GLUT-1) or accumulation of glucose (Kumagai, 1999;Lorenzi et al, 1986) within the retina or its microvasculature (Kador et al, 1988;Kern and Engerman, 1986;Mizutani et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

Comparison of Glucose Influx and Blood Flow in Retina and Brain of Diabetic Rats

Puchowicz

Magness

et al. 2004

J Cereb Blood Flow Metab

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Summary:Diabetes is associated with extensive microvascular pathology and decreased expression of the glucose transporter (GLUT-1) in retina, but not brain. To explore the basis of these differences, the authors simultaneously measured glucose influx (mol · g −1 · min) and blood flow (mL · g −1 · min −1 ) in retina and brain cortex of nondiabetic control rats (normoglycemic and acute-hyperglycemic) and in rats with streptozotocin-induced diabetes (with or without aminoguanidine (AMG) treatment) using a single-pass, dual-label indicator method. In addition, tissue glucose and adenosine triphosphate (nmol/mg dry weight) levels were measured. Glucose influx in retina exceeded that of cortex by about threefold for both the nondiabetic and diabetic groups. In contrast, blood flow in retina was significantly lower than in cortex by about threefold for each group. Retinal and cortical glucose influx in the diabetic rats was lower than in the nondiabetic acute-hyperglycemic group, but not in the normoglycemic group. Blood flow in these tissues remained relatively unchanged with glycemic conditions. The glucose levels in the diabetic retina (aminoguanidine untreated and aminoguanidine treated) were fourfold to sixfold greater than the nondiabetic retina. The cortical glucose levels remained unchanged in all groups. These data suggest that the accumulation of glucose in the diabetic retina cannot be explained by increased endothelialglucose uptake or increased vascular membrane permeability.

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“…Retina and cerebral cortex are embryologically similar, yet, we and others (9)(10)(11) have found them to differ in their susceptibility to develop microvascular lesions of diabetes. Unlike the extensive microvascular pathology that develops in retinal capillaries in diabetes, cerebral capillaries show no increase in the number of acellular capillaries, microaneurysms, or pericyte ghosts (11).…”

mentioning

confidence: 99%

Diabetes downregulates GLUT1 expression in the retina and its microvessels but not in the cerebral cortex or its microvessels.

et al. 2000

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Capillaries in the retina are more susceptible to develop microvascular lesions in diabetes than capillaries in the embryologically similar cerebral cortex. Because available evidence implicates hyperglycemia in the pathogenesis of diabetic retinopathy, differences in glucose transport into the retina and brain might contribute to this observed tissue difference in susceptibility to diabetes-induced microvascular disease. Thus, we compared levels of GLUT1 and GLUT3 expression in the retina, cerebrum, and their respective microvessels by Western blot analysis. In nondiabetic animals, the content of GLUT1 protein in retina and its microvessels was multifold greater than that of cerebral cortex gray matter and its microvessels. Streptozotocin-induced diabetes of a 2-week or 2-month duration reduced GLUT1 expression in the retina and its microvasculature bỹ 50%, but it resulted in no reduction in GLUT1 expression in cerebrum or its microvessels. The density of capillaries in retinas of diabetic animals did not change from normal, and so the observed decrease in GLUT1 expression in the retina and retinal capillaries of diabetic animals cannot be attributed to fewer vessels. Despite the diabetes-induced reduction of GLUT1 expression in retina, neural retina of diabetic rats still possessed more GLUT1 than the cerebrum. Retinal pigment epithelium (RPE) possessed more GLUT1 than neural retina or its microvessels, and expression of the transporter in the RPE was not affected by diabetes. GLUT3 levels were greater in cerebral gray matter than in retina, and they were unaffected by diabetes in either tissue. The effect of diabetes on GLUT1 expression differs between retina and cerebral cortex, suggesting that glucose transport is regulated differently in these embryologically similar tissues. Because diabetes results in downregulation of GLUT1 expression in retinal microvessels, but not in RPE, the fraction of the glucose entering the retina in diabetes is likely to be greater across the RPE than across the retinal vasculature. Diabetes 49:1016-1021, 2000 H yperglycemia is sufficient to initiate the development of diabetic retinopathy. This fact has been made especially clear by the development of diabetic-like retinopathy in normal nondiabetic dogs and rodents that were experimentally made hyperglycemic by feeding them a diet enriched with galactose (1-5). Studies demonstrating that intensive therapy sufficient to minimize hyperglycemia inhibits the development of retinopathy (6-8) are consistent with the evidence that hyperglycemia plays a critical role in the pathogenesis of retinal disease. However, the mechanism by which hyperglycemia causes diabetic retinopathy remains unclear. Excessive transport or concentration of glucose within cells of the retina is a common thread underlying most of the biochemical mechanisms that have been postulated to play a role in the pathogenesis of diabetic retinopathy.Retina and cerebral cortex are embryologically similar, yet, we and others (9-11) have found them to differ in their sus...

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Degeneration of Intramural Pericytes in Diabetic Retinopathy

Cited by 85 publications

References 10 publications

The Effect of Neovascularization on Human Retinal Pigment Epithelium after Hyperbaric Oxygen Therapy

The Effect of Neovascularization on Human Retinal Pigment Epithelium after Hyperbaric Oxygen Therapy

Comparison of Glucose Influx and Blood Flow in Retina and Brain of Diabetic Rats

Diabetes downregulates GLUT1 expression in the retina and its microvessels but not in the cerebral cortex or its microvessels.

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