Diabetic retinopathy: hyperglycaemia, oxidative stress and beyond

Abstract

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

Neurodegeneration in diabetic retinopathy: does it really matter?

“…This so-called vasodegeneration or vasoregression is a central pathogenic response to chronic hyperglycaemia and initiates the progressive ischaemia characteristic of diabetic retinopathy. The importance of vasoregression in the setting of diabetic retinopathy has been comprehensively reviewed by Hammes et al [39, 40] and is conceptually divided into sequential steps: branch selection by flow dichotomy; vessel constriction; occlusion; endothelial retraction/apoptosis/reintegration; and resolution of the remaining empty vascular basement-membrane tube. Blood flow is a critical determinant of endothelial cell damage and sustained, abnormal autoregulatory responses are likely to significantly contribute to vasoregression.…”

Knockdown of ALK7 inhibits high glucose‐induced oxidative stress and apoptosis in retinal pigment epithelial cells

“…Hyperglycaemia remains the most widely-recognized systemic factor contributing to the onset and progression of early DR. 3 Prolonged hyperglycaemia results in altered insulin action, and thereby perturbs the metabolism of carbohydrate, fat and protein, which may contribute directly to retinopathy. 3 In addition to these, the effects of hyperglycaemia on DR are mostly indirect. Prolonged HG condition also results in the overproduction of ROS, which can be attributed to increased glucose metabolism by the glycolysis and citric acid cycle pathways.…”

“…In the past decades, research on the pathophysiology and management of DR have revolutionized the understanding of this disease. It has been reported that a number of interconnected biochemical mechanisms associated with hyperglycaemia have been implicated in the pathogenesis of DR . Prolonged elevation of blood glucose induces the production of reactive oxygen species (ROS) and advanced glycation end‐products (AGEs) .…”

“…1,2 In the past decades, research on the pathophysiology and management of DR have revolutionized the understanding of this disease. It has been reported that a number of interconnected biochemical mechanisms associated with hyperglycaemia have been implicated in the pathogenesis of DR. 3 Prolonged elevation of blood glucose induces the production of reactive oxygen species (ROS) and advanced glycation end-products (AGEs). 4,5 The products in turn trigger multiple cellular signalling pathways, leading to the oxidative stress and inflammatory response, which contribute to the disruption of normal cellular physiology.…”

Lipoprotein‐associated phospholipase A2: The story continues

“…Diabetic retinopathy (DR) is classified as a microvascular complication of DM, which is the major cause of partial and complete vision loss in diabetic patients. The features of DR include the loss of ECs and pericytes of retinal capillaries, breakdown and leakage of the blood‐retinal barrier (BRB), formation of acellular capillaries, and neovascularization . On the basis of the proliferative status of the retinal vasculature, DR has been divided into two stages: a nonproliferative stage (NPDR), characterized by microaneurysms, retinal hemorrhages, vascular tortuosity, and hard exudates; and a proliferative stage (PDR), characterized by the creation of new but leaky blood vessels .…”