The neurovascular unit and the pathophysiologic basis of diabetic retinopathy

Gardner, Thomas W.; Dávila, José

doi:10.1007/s00417-016-3548-y

Cited by 147 publications

(122 citation statements)

References 32 publications

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“…Advances in understanding early cellular changes in the diabetic retina combined with improved retinal imaging have led to a conceptualization that DR can be viewed as a disease of the retinal neurovascular unit (Figure 2), which refers to the functional coupling and interdependency of neurons, glia, and vasculature (4) that integrate to regulate normal retinal function (61). An important facet of this integration is the coordination of local blood flow changes with fluctuations in metabolic demands.…”

Section: The Neurovascular Unit: a Framework For Understanding Drmentioning

confidence: 99%

Diabetic retinopathy: current understanding, mechanisms, and treatment strategies

Duh¹,

Sun²,

Stitt³

2017

JCI Insight

768

648

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Section: The Neurovascular Unit: a Framework For Understanding Drmentioning

confidence: 99%

Diabetic retinopathy: current understanding, mechanisms, and treatment strategies

Duh¹,

Sun²,

Stitt³

2017

JCI Insight

768

648

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“…For instance, the response to functional hyperaemia, which is critical for supplying oxygen and glucose to the active retinal neurons in the inner and middle retinal layers, becomes impaired as diabetes progresses. This response can be examined by flicker-evoked vasodilation, which is decreased in individuals in the early stages of diabetic retinopathy, even before overt signs of clinical retinopathy are observed [20–25]. These changes clearly demonstrate the relevance of neurovascular coupling or, in other words, interactions between the neurosensory retina and its blood vessels.…”

Section: The Key Role Of the Nvu In Retinal Physiologymentioning

confidence: 99%

Neurodegeneration in diabetic retinopathy: does it really matter?

2018

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The concept of diabetic retinopathy as a microvascular disease has evolved, in that it is now considered a more complex diabetic complication in which neurodegeneration plays a significant role. In this article we provide a critical overview of the role of microvascular abnormalities and neurodegeneration in the pathogenesis of diabetic retinopathy. A special emphasis is placed on the pathophysiology of the neurovascular unit (NVU), including the contributions of microvascular and neural elements. The potential mechanisms linking retinal neurodegeneration and early microvascular impairment, and the effects of neuroprotective drugs are summarised. Additionally, we discuss how the assessment of retinal neurodegeneration could be an important index of cognitive status, thus helping to identify individuals at risk of dementia, which will impact on current procedures for diabetes management. We conclude that glial, neural and microvascular dysfunction are interdependent and essential for the development of diabetic retinopathy. Despite this intricate relationship, retinal neurodegeneration is a critical endpoint and neuroprotection, itself, can be considered a therapeutic target, independently of its potential impact on microvascular disease. In addition, interventional studies targeting pathogenic pathways that impact the NVU are needed. Findings from these studies will be crucial, not only for increasing our understanding of diabetic retinopathy, but also to help to implement a timely and efficient personalised medicine approach for treating this diabetic complication.Electronic supplementary materialThe online version of this article (10.1007/s00125-018-4692-1) contains a slideset of the figures for download, which is available to authorised users.

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“…Diabetic retinopathy is characterised by morphological lesions developing secondary to disturbances in retinal blood flow [1,2]. Pharmacological interventions against these disturbances are challenged by opposite changes in blood flow within the same eye, with hyperperfusion in the macular area and capillary occlusion in the retinal periphery.…”

Section: Introductionmentioning

confidence: 99%

Dilatation of Retinal Arterioles Induced by Topical Dorzolamide for One Week Is Impaired in Patients with Type 1 Diabetes and Mild Retinopathy

Tilma

Bek

2019

Ophthalmologica

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Background: Diabetic retinopathy is characterised by morphological lesions in the retina secondary to disturbances in retinal blood flow. Previous studies have shown that the carbonic anhydrase inhibitor (CAI) dorzolamide can induce immediate dilatation of retinal arterioles and a sustained increase in retinal blood flow in primary open-angle glaucoma. However, the effect of sustained treatment with CAI on retinal arterioles in normal persons and in patients with diabetic retinopathy is unknown. Methods: The Dynamic Vessel Analyzer was used to assess the baseline diameter and the diameter response of retinal arterioles during an increase in arterial blood pressure induced by isometric exercise and during flicker stimulation before and 2 h, 24 h and 1 week after onset of topical treatment with dorzolamide. At each examination the diameter responses were studied before and during breathing in of a hypercapnic gas mixture. Results: Treatment with dorzolamide for 1 week significantly increased the diameter of retinal arterioles in normal persons, and breathing in of a hypercapnic gas mixture reduced this response. The pathological vasodilatation and reduced retinal autoregulation in patients with diabetic retinopathy were unaffected by dorzolamide and hypercapnia. Conclusions: The study suggests a lack of relevance of CAI for the treatment of pathological vasodilatation in early diabetic retinopathy.

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The neurovascular unit and the pathophysiologic basis of diabetic retinopathy

Cited by 147 publications

References 32 publications

Diabetic retinopathy: current understanding, mechanisms, and treatment strategies

Diabetic retinopathy: current understanding, mechanisms, and treatment strategies

Neurodegeneration in diabetic retinopathy: does it really matter?

Dilatation of Retinal Arterioles Induced by Topical Dorzolamide for One Week Is Impaired in Patients with Type 1 Diabetes and Mild Retinopathy

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