Diabetic Retinopathy: Targeting Vasoregression

Hammes, Hans Peter; Feng, Yuxi; Pfister, Frederick; Brownlee, Michael

doi:10.2337/db10-0454

Cited by 312 publications

(281 citation statements)

References 62 publications

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“…Vasoregression (the formation of acellular capillaries) is probably the most important early lesion in the early diabetic retina [26,27]. Understanding the mechanisms that contribute to vasoregression is essential for its prevention, and physiological vasoregression acts as a good example from which we can learn about inborn programming that is reactivated during incipient disease stages.…”

Section: The Importance Of Vasoregressionmentioning

confidence: 99%

“…a low number of apoptotic cells in relation to the magnitude of vasoregression, and no resolution of empty basement membranes). Migration (and to a lesser extent apoptosis) leads to pericyte loss in remodelling capillaries of animal models but persistence of pericytes on denuded capillary segments is more prevalent in human retinas [26,41]. Neuronal dysfunction, measured by electroretinography, is evident after 6 weeks, while structural changes indicating neurodegeneration appear only after 6 months [42].…”

Section: Modelling Early Diabetic Retinopathymentioning

confidence: 99%

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Diabetic retinopathy: hyperglycaemia, oxidative stress and beyond

2017

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Diabetic retinopathy remains a relevant clinical problem. In parallel with diagnostic and therapeutic improvements, the role of glycaemia and reactive metabolites causing cell stress and biochemical abnormalities as treatment targets needs continuous re-evaluation. Furthermore, the basic mechanisms of physiological angiogenesis, remodelling and pruning give important clues about the origins of vasoregression during the very early stages of diabetic retinopathy and can be modelled in animals. This review summarises evidence supporting a role for the neurovascular unit-composed of neuronal, glial and vascular cells-as a responder to the biochemical changes imposed by reactive metabolites and high glucose. Normoglycaemic animal models developing retinal degeneration, provide valuable information about common pathways downstream of progressive neuronal damage that induce vasoregression, as in diabetic models. These models can serve to assess novel treatments addressing the entire neurovascular unit for the benefit of early diabetic retinopathy. Diabetic retinopathy: the danger is not overThe overall prevalence of diabetic retinopathy is 35% among people with diabetes worldwide, with a current decline in both any retinopathy and sight-threatening stages [1]. Diabetic retinopathy ranks fifth among common causes for blindness or severe vision impairment and a recent meta-analysis revealed that the age-standardised prevalence of diabetic retinopathyrelated blindness will increase due to increasing populations and average age together with a reduction in death rates [2]. Lending support to the magnitude of the problem are reports that even when a person first presents at screening services, advanced diabetic retinopathy is present at levels that are no longer amenable to medical interventions [3,4]. Recent population-based studies from Europe revealed that screening-detected diabetic retinopathy appeared in more thanElectronic supplementary material The online version of this article (https://doi

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Section: The Importance Of Vasoregressionmentioning

confidence: 99%

Section: Modelling Early Diabetic Retinopathymentioning

confidence: 99%

Diabetic retinopathy: hyperglycaemia, oxidative stress and beyond

2017

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“…14,15 Specialized endothelial cells (the so-called 'tip' cells) lead the process along the VEGF-A gradient. 7,8,16 It was recently…”

Section: Introductionmentioning

confidence: 99%

“…These tube-like structures are stabilized and become capillaries by Ang-1-mediated recruitment of pericytes and basement membrane deposition. 8,16,26 Arteriogenesis, however, is a further development of these capillaries into larger vessels like arterioles and venules or remodeling and maturation of already existing collateral arterioles that are subjected to low flow conditions under normal conditions. Unlike angiogenesis, arteriogenesis occurs in the normoxic tissue surrounding the ischemic area, triggered by increased fluid shear stress as a result of blood flow redistribution after vessel occlusion.…”

Section: Introductionmentioning

confidence: 99%

Cerebral Neovascularization in Diabetes: Implications for Stroke Recovery and beyond

Ergul

Abdelsaid

Fouda

et al. 2014

J Cereb Blood Flow Metab

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Neovascularization is an innate physiologic response by which tissues respond to various stimuli through collateral remodeling (arteriogenesis) and new vessel formation from existing vessels (angiogenesis) or from endothelial progenitor cells (vasculogenesis). Diabetes has a major impact on the neovascularization process but the response varies between different organ systems. While excessive angiogenesis complicates diabetic retinopathy, impaired neovascularization contributes to coronary and peripheral complications of diabetes. How diabetes influences cerebral neovascularization remained unresolved until recently. Diabetes is also a major risk factor for stroke and poor recovery after stroke. In this review, we discuss the impact of diabetes, stroke, and diabetic stroke on cerebral neovascularization, explore potential mechanisms involved in diabetes-mediated neovascularization as well as the effects of the diabetic milieu on poststroke neovascularization and recovery, and finally discuss the clinical implications of these effects.

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“…4,8,13 Different outcomes of neovascularization attributed to DM have been found in various organ systems. 1,10,19,26 The effect of DM on cerebral neovascularization remains unclear. In this study, we sought to investigate the effect of EDAS on clinical outcomes and explore the distinction of collateral circulation between MMD patients with and without type 2 diabetes mellitus (T2DM).…”

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confidence: 99%

Surgical outcomes following encephaloduroarteriosynangiosis in adult moyamoya disease associated with Type 2 diabetes

Ren

Zhang

Liu

et al. 2016

JNS

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M oyaMoya disease (MMD), a cerebral vascular disease, is characterized by progressive stenosis and occlusion of the terminal portion of the bilateral internal carotid arteries, leading to the formation of an abnormal vascular network composed of collateral pathways at the base of the brain. MMD can cause a reduction in the blood supply to the brain, and there are 2 major etiological categories of symptoms: those due to brain ischemia (i.e., stroke, transient ischemic attack, and seizure) and those due to the deleterious consequences of the compensatory mechanisms in response to ischemia (i.e., hemorrhage from fragile collateral vessels and headache aBBreViatiONS CBF = cerebral blood flow; DM = diabetes mellitus; EDAS = encephaloduroarteriosynangiosis; MCA = middle cerebral artery; MMD = moyamoya disease; mRS = modified Rankin Scale; PCA = posterior cerebral artery; STA = superficial temporal artery; T2DM = Type 2 DM. SuBmitted January 29, 2015. OBJectiVe Debate exists regarding the merits and shortcomings of an indirect bypass procedure for treating adult patients with moyamoya disease (MMD). Considerable variation in neovascularization occurs among different organs in patients with diabetes mellitus. Here, the effect of encephaloduroarteriosynangiosis on MMD associated with Type 2 diabetes mellitus (T2DM) is evaluated. methOdS A retrospective and 1:2 matched case-control study was conducted in moyamoya patients with or without T2DM (n = 180). Postoperative collateral formations were graded according to the Modified Collateral Grading System that originated from the Matsushima Angiographic Stage Classification. Neurological function outcomes before and after the operation were evaluated according to the modified Rankin Scale. Univariate and multivariate logistic regression analyses were performed to determine the risk factors for clinical outcome. reSultS There was no statistically significant difference in the constituent ratios of initial symptom and preoperative Suzuki stage between patients with and without T2DM. Progression of angiopathy around the circle of Willis was postoperatively observed in bilateral internal carotid arteries in both groups. Patients with T2DM had a higher postoperative Suzuki stage (p < 0.01) and more frequent development of collateral angiogenesis germinating from the external carotid after indirect revascularization procedures in the surgical cerebral hemisphere (82.7% vs 72.2%; p < 0.05). The extent of postoperative collateral formation in patients with diabetes mellitus was significantly higher (p < 0.01). Postoperative clinical improvement in the diabetes group was more common after revascularization procedures (p < 0.05), and the diabetes group had lower modified Rankin Scale scores (p < 0.05) in comparison with the nondiabetes group. Late postoperative stroke and posterior cerebral artery involvement were identified as predictors of unfavorable clinical outcome in both groups, while T2DM was associated with a favorable clinical outcome. cONcluSiONS Encephaloduroarteriosynangio...

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Diabetic Retinopathy: Targeting Vasoregression

Cited by 312 publications

References 62 publications

Diabetic retinopathy: hyperglycaemia, oxidative stress and beyond

Diabetic retinopathy: hyperglycaemia, oxidative stress and beyond

Cerebral Neovascularization in Diabetes: Implications for Stroke Recovery and beyond

Surgical outcomes following encephaloduroarteriosynangiosis in adult moyamoya disease associated with Type 2 diabetes

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