Diabetic Retinopathy

Neely, Kimberly A.; Quillen, David A.; Schachat, Andrew P.; Gardner, Thomas W.; Blankenship, George W.

doi:10.1016/s0025-7125(05)70027-4

Cited by 34 publications

(24 citation statements)

References 53 publications

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“…Since the initial observation of capillary microaneurysms by MacKenzie and Nettleship in 1879 (128), abnormalities of the retinal vasculature have been known to play a central role in the pathogenesis of diabetic retinopathy. The loss of microvascular cells is an early event in diabetic retinopathy that leads to a loss of perfusion and eventual hypoxia (126,127,129,130). Hypoxia in turn induces the expression of angiogenic factors as a compensatory reaction leading to the next phase, proliferative diabetic retinopathy.…”

Section: Retinopathymentioning

confidence: 99%

Diabetic complications and dysregulated innate immunity

Graves

Kayal²

2008

Front Biosci

223

188

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Diabetes mellitus is a metabolic disorder that leads to the development of a number of complications. The etiology of each diabetic complication is undoubtedly multifactorial. We will focus on one potential component that may be common in many diabetic complications, dysregulation of innate immunity associated with an increased inflammatory response. High glucose levels lead to shunting through the polyol pathway, an increase in diacylglycerol which activates protein kinase C, an increase in the release of electrons that react with oxygen molecules to form superoxides, and the non-enzymatic glycosylation of proteins that result in greater formation of advanced glycation end products. Each of these can lead to aberrant cell signalling that affects innate immunity for example, by activating the MAP kinase pathway or inducing activation of transcription factors such as NF-kappaB. This may be a common feature of several complications including periodontal disease, atherosclerosis, nephropathy, impaired healing and retinopathy. These complications are frequently associated with increased expression of inflammatory cytokines such as TNF-alpha, IL-1beta and IL-6 and enhanced generation of reactive oxygen species. Cause and effect relationship between dysregulation of key components of innate immunity and diabetic complications in many instances have been demonstrated with the use of cytokine blockers and antioxidants.

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Section: Retinopathymentioning

confidence: 99%

Diabetic complications and dysregulated innate immunity

Graves

Kayal²

2008

Front Biosci

223

188

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“…Nearly all people with type I and more than half with type II diabetes develop complications involving the retina (Fong et al, 2003). Clinically, diabetic retinopathy can be classified as background retinopathy (BDR), preproliferative retinopathy (PPDR), and proliferative retinopathy (PDR) (Alder et al, 1997;Davis, 1992;Hudson, 1996;Neely et al, 1998). BDR is the earliest stage, which is character-ized by capillary basement membrane thickening, pericyte loss, microaneurysms, increased permeability, exudate deposits, and retinal microinfarcts.…”

Section: Introductionmentioning

confidence: 99%

Growth Factors in Proliferative Diabetic Retinopathy

Khan

Chakrabarti

2003

Journal of Diabetes Research

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Many growth factors are implicated in the pathogenesis of proliferative diabetic retinopathy. Alteration of growth factors and their receptors in diabetes has been shown in both experimental and clinical studies. Sustained hyperglycemia resulting from long-standing diabetes leads to several biochemical abnormalities that consequently result in retinal hypoxia. Retinal oxygenation state regulates various growth factors that promote angiogenesis in order to meet the oxygen demands of the tissue. However, unregulated expression of these growth factors and induction of complex cascades leading to augmentation of other proangiogenic factors, which may not be regulated by tissue oxygenation, leads to uncontrolled retinal neovascularization and blindness in diabetic patients.

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“…iabetes affects nearly 16 million people in the U.S. alone, and diabetic retinopathy, the principal ocular complication, remains the leading cause of vision loss between the second and seventh decades of life (1)(2)(3). Diabetes-associated changes in retinal physiology precede clinically detectable changes in the retinal vasculature, and experimental evidence from studies of human diabetes and animal models of hyperglycemia suggest that these early changes involve Mü ller cells, the principal retinal glia.…”

mentioning

confidence: 99%

Changes in IGF Activities in Human Diabetic Vitreous

et al. 2004

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Mü ller cells, the principal glia of the retina, generate tractional forces in response to IGF-I and plateletderived growth factor and are present in diabetic fibrovascular scar tissues causing traction retinal detachment. While diabetes-associated increases in vitreous IGFs have been reported, paradoxically high concentrations of these same growth factors in normal vitreous suggest the presence of more complex mechanisms regulating growth factor bioavailability. To define diabetes-associated changes in vitreous biological activity, the stimulatory effects of 68 samples were evaluated using Mü ller cell tractional force generation as a target bioassay. Dose-response profiles were used to calculate vitreous specific activity (per unit protein) and total vitreous activity (per unit volume). Vitreous samples from patients lacking diabetes or other retinal pathology had undetectable or low activities, whereas diabetic retinopathy was associated with 6.9-and 8.7-fold increases in vitreous specific and total activities, respectively. Secondary analyses revealed no activity differences associated with patient sex, age, or the presence of vitreous hemorrhage. However, compared with diabetes alone, the presence of proliferative diabetic retinopathy was associated with additional 2.3-fold increases in vitreous specific and total activities. Vitreous dose-response assays performed with and without growth factor-neutralizing antibodies enable attribution of vitreous activity to IGFs (53.9%) and, to a lesser extent, platelet-derived growth factors (14.5%). Because the observed increases in vitreous growth factor activity grossly exceed the reported increases in growth factor concentration, these data indicate that diabetes-associated changes in vitreous biological activity involve more complex biochemical changes that ultimately yield increased growth factor bioavailability and/or Mü ller cell responsiveness. Diabetes 53: 2428 -2435, 2004

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Diabetic Retinopathy

Cited by 34 publications

References 53 publications

Diabetic complications and dysregulated innate immunity

Diabetic complications and dysregulated innate immunity

Growth Factors in Proliferative Diabetic Retinopathy

Changes in IGF Activities in Human Diabetic Vitreous

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