Pericytes, inflammation, and diabetic retinopathy

Spencer, Benjamin G; Estevez, José; Liu, Ebony; Craig, Jamie E; Finnie, John

doi:10.1007/s10787-019-00647-9

Cited by 75 publications

(57 citation statements)

References 87 publications

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“…Diabetes causes increased local and systemic production of numerous inflammatory molecules involved in DR development such as vascular adhesion molecules, cytokines, chemokines, transcription, and growth factors ( 5 , 9 - 15 , 18 - 42 ). Elevated concentrations of these molecules induce activation and migration of leukocytes and leukostasis ( 4 , 40 , 41 ) with subsequent capillary occlusion, retinal hypoxia, and endothelial cell damage.…”

Section: Inflammation and Diabetic Retinopathymentioning

confidence: 99%

“…Activated pericytes are also involved in the retinal inflammatory processes of DR development. They excrete pro-inflammatory mediators, which direct and accumulate immune cells towards the site of retinal inflammation ( 42 ). There is growing evidence that retinal neurodegeneration may be a relevant pathophysiological mechanism of DR development ( 10 , 31 , 43 ).…”

Section: Inflammation and Diabetic Retinopathymentioning

confidence: 99%

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Inflammatory and angiogenic biomarkers in diabetic retinopathy

Kaštelan

Orešković

Bišćan

et al. 2020

Biochem. med. (Online)

112

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Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes mellitus (DM) and a leading cause of blindness in working-age adults in developed countries. Numerous investigations have recognised inflammation and angiogenesis as important factors in the development of this complication of diabetes. Current methods of DR treatment are predominantly used at advanced stages of the disease and could be associated with serious side effects. Therefore, new diagnostic methods are needed in order to identify the initial stages of DR as well as monitoring the effects of applied therapy. Biochemical biomarkers are molecules found in blood or other biological fluid and tissue that indicate the existence of an abnormal condition or disease. They could be a valuable tool in detecting early stages of DR, identifying patients most susceptible to retinopathy progression and monitoring treatment outcomes. Biomarkers related to DR can be measured in the blood, retina, vitreous, aqueous humour and recently in tears. As the retina represents a small part of total body mass, a circulating biomarker for DR needs to be highly specific. Local biomarkers are more reliable as indicators of the retinal pathology; however, obtaining a sample of aqueous humour, vitreous or retina is an invasive procedure with potential serious complications. As a non-invasive novel method, tear analysis offers a promising direction in further research for DR biomarker detection. The aim of this paper is to review systemic and local inflammatory and angiogenic biomarkers relevant to this sight threatening diabetic complication.

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Section: Inflammation and Diabetic Retinopathymentioning

confidence: 99%

Section: Inflammation and Diabetic Retinopathymentioning

confidence: 99%

Inflammatory and angiogenic biomarkers in diabetic retinopathy

Kaštelan

Orešković

Bišćan

et al. 2020

Biochem. med. (Online)

112

View full text Add to dashboard Cite

show abstract

“…Although etiologically different, both conditions are characterized by hyperglycemia and dyslipidemia which are considered major risk factors for development of the shared macrovascular and microvascular complications as well as neurological dysfunction ( 15 ); moreover, the two conditions can co-exist ( 4 ). The pathobiology of both T1D and T2D and their macrovascular complications is grounded in inflammation but there is greater debate concerning microvascular disease ( 16 , 17 ). For instance, diabetic peripheral neuropathy, nephropathy, and retinopathy are microvascular complications in which small vessel endothelial cells seem to be the focus of the attack ( 18 , 19 ).…”

Section: Introductionmentioning

confidence: 99%

The Role of Inflammation in Diabetic Retinopathy

2020

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Inflammation is central to pathogenic processes in diabetes mellitus and the metabolic syndrome and particularly implicates innate immunity in the development of complications. Inflammation is a primary event in Type 1 diabetes where infectious (viral) and/or autoimmune processes initiate disease; in contrast, chronic inflammation is typical in Type 2 diabetes and is considered a sequel to increasing insulin resistance and disturbed glucose metabolism. Diabetic retinopathy (DR) is perceived as a vascular and neurodegenerative disease which occurs after some years of poorly controlled diabetes. However, many of the clinical features of DR are late events and reflect the nature of the retinal architecture and its cellular composition. Retinal microvascular disease is, in fact, an early event pathogenetically, induced by low grade, persistent leukocyte activation which causes repeated episodes of capillary occlusion and, progressive, attritional retinal ischemia. The later, overt clinical signs of DR are a consequence of the retinal ischemia. Metabolic dysregulation involving both lipid and glucose metabolism may lead to leukocyte activation. On a molecular level, we have shown that macrophage-restricted protein tyrosine phosphatase 1B (PTP1B) is a key regulator of inflammation in the metabolic syndrome involving insulin resistance and it is possible that PTP1B dysregulation may underlie retinal microvascular disease. We have also shown that adherent CCR5 + CD11b + monocyte macrophages appear to be selectively involved in retinal microvascular occlusion. In this review, we discuss the relationship between early leukocyte activation and the later features of DR, common pathogenetic processes between diabetic microvascular disease and other vascular retinopathies, the mechanisms whereby leukocyte activation is induced in hyperglycemia and dyslipidemia, the signaling mechanisms involved in diabetic microvascular disease, and possible interventions which may prevent these retinopathies. We also address a possible role for adaptive immunity in DR. Although significant improvements in treatment of DR have been made with intravitreal anti-VEGF therapy, a sizeable proportion of patients, particularly with sight-threatening macular edema, fail to respond. Alternative therapies targeting inflammatory processes may offer an advantage.

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“…Chronic low-grade subclinical inflammation in the state of persistent hyperglycemia has an effect on retinal microvascular and eventually leads to DR. [3] Aberrant neovascularization following retinal ischemia is a clinical feature of PDR, which can lead to vitreous hemorrhage and tractional retinal detachment, thus affecting vision [4]. Several studies have indicated that inflammatory mediators were involved in DR, and inflammatory cells produced angiogenic cytokines and growth factors, which were implicated in the progression of DR [5][6][7].…”

Section: Introductionmentioning

confidence: 99%

Elevated vitreous Lipocalin-2 levels of patients with proliferative diabetic retinopathy

Wang

Liu

et al. 2020

BMC Ophthalmol

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Background: Lipocalin-2 (LCN2) is a novel adipokine with potential roles in obesity, insulin resistance, and inflammation. This study aims to assess the concentrations of LCN2 and vascular endothelial growth factor (VEGF) expressed in the vitreous humors of patients with proliferative diabetic retinopathy (PDR). Methods: The concentrations of LCN2 and VEGF were measured from the vitreous of 67 patients undergoing vitrectomy (20 controls and 47 PDR) via enzyme-linked immunosorbent assay (ELISA). Patients with non-ocular pathology that could elevate the LCN2 level in the vitreous were excluded. PDR activity and a history of panretinal photocoagulation were used for further grouping analysis. Results: The vitreous concentration of LCN2 was statistically significantly higher in the PDR group compared to the control group (63,522 (30,009) pg/ml versus 1663 (1191) pg/ml, respectively; P < 0.001). VEGF level was also significantly higher in the PDR group than in the control group (1038 (1326) pg/ml versus 9 pg/ml, respectively; P < 0.001). The mean vitreous LCN2 and VEGF levels in active PDR patients were significantly higher than that of the inactive PDR patients. The mean LCN2 concentration in vitreous humor was significantly lower in the 28 PDR patients with a history of complete PRP (37,304 (16,651) pg/mL) in comparison with 19 PDR patients without preperformed panretinal photocoagulation or with preperformed incomplete panretinal photocoagulation (79,796 (24,391) pg/mL). A significant correlation between the vitreous LCN2 level and VEGF level was found in patients with PDR (R = 0.34; P = 0.019). Conclusions: This report shows a significant increase of LCN2 in the vitreous fluid of patients with PDR and present a significant correlation between LCN2 and VEGF, suggesting LCN2 might be involved in the pathogenesis of PDR.

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Pericytes, inflammation, and diabetic retinopathy

Cited by 75 publications

References 87 publications

Inflammatory and angiogenic biomarkers in diabetic retinopathy

Inflammatory and angiogenic biomarkers in diabetic retinopathy

The Role of Inflammation in Diabetic Retinopathy

Elevated vitreous Lipocalin-2 levels of patients with proliferative diabetic retinopathy

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