Role of Inflammation in Diabetic Retinopathy

International Journal of Molecular Sciences, Journal Year: 2018, Volume and Issue: 19(4), P. 942 - 942

Published: March 22, 2018

Diabetic retinopathy is a common complication of diabetes and remains the leading cause blindness among working-age population. For decades, diabetic was considered only microvascular complication, but retinal microvasculature intimately associated with governed by neurons glia, which are affected even prior to clinically detectable vascular lesions. While progress has been made improve alterations, there still no treatment counteract early neuro-glial perturbations in retinopathy. Diabetes complex metabolic disorder, characterized chronic hyperglycemia along dyslipidemia, hypoinsulinemia hypertension. Increasing evidence points inflammation as one key player diabetes-associated perturbations, however, exact underlying molecular mechanisms not yet fully understood. Interlinked pathways, such oxidative stress, formation advanced glycation end-products increased expression endothelial growth factor have received lot attention they all contribute inflammatory response. In current review, we focus on involvement pathophysiology special emphasis functional relationships between glial cells neurons. Finally, summarize recent advances using novel targets inhibit

Language: Английский

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Efficacy, durability, and safety of intravitreal faricimab with extended dosing up to every 16 weeks in patients with diabetic macular oedema (YOSEMITE and RHINE): two randomised, double-masked, phase 3 trials

The Lancet, Journal Year: 2022, Volume and Issue: 399(10326), P. 741 - 755

Published: Jan. 24, 2022

Language: Английский

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OCT Angiography Metrics Predict Progression of Diabetic Retinopathy and Development of Diabetic Macular Edema

Ophthalmology, Journal Year: 2019, Volume and Issue: 126(12), P. 1675 - 1684

Published: June 26, 2019

Language: Английский

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Guidelines for the Management of Retinal Vein Occlusion by the European Society of Retina Specialists (EURETINA)

Ophthalmologica, Journal Year: 2019, Volume and Issue: 242(3), P. 123 - 162

Published: Jan. 1, 2019

The high prevalence of cardiovascular disease particularly in the elderly population is associated with retinal vascular disease. Retinal vein occlusions represent severe disturbances hypoxia-sensitive neurosensory retina. Acute and excessive leakage leads to diagnostic hallmarks hemorrhage edema substantial thickening. Advanced tools such as OCT angiography allow evaluate ischemia identify risk for late complications will soon reach clinical routine besides fluorescein angiography. Accordingly, duration non-perfusion a crucial prognostic factor requiring timely therapeutic intervention. With immediate inhibition leakage, anti-VEGF substances excel treatment choice. Multiple trials optimal potential functional benefit or lesser regenerative spectrum have evaluated aflibercept, ranibizumab, bevacizumab. As occlusion chronic disease, long-term monitoring should be individualized combine maintenance practicability. While steroids may considered patients systemic risk, surgery remains advisable only very few patients. Destructive laser an option if reliable not feasible. Ophthalmologists are also advised perform basic workup recognize concomitants. current edition EURETINA guidelines highlights state-of-the-art recommendations based on literature expert opinions occlusion.

Language: Английский

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Pathophysiology of Diabetic Retinopathy: The Old and the New

Diabetes & Metabolism Journal, Journal Year: 2018, Volume and Issue: 42(5), P. 364 - 364

Published: Jan. 1, 2018

Vision loss in diabetic retinopathy (DR) is ascribed primarily to retinal vascular abnormalities—including hyperpermeability, hypoperfusion, and neoangiogenesis—that eventually lead anatomical functional alterations neurons glial cells. Recent advances imaging systems using optical coherence tomography technologies pharmacological treatments anti-vascular endothelial growth factor drugs corticosteroids have revolutionized the clinical management of DR. However, cellular molecular mechanisms underlying pathophysiology DR are not fully determined, largely because hyperglycemic animal models only reproduce limited aspects subclinical early Conversely, non-diabetic mouse that represent hallmark disorders DR, such as pericyte deficiency ischemia, provided clues toward an understanding sequential events responsible for vision-impairing conditions. In this review, we summarize manifestations treatment modalities discuss current emerging concepts with regard introduce perspectives on development new drugs, emphasizing breakdown blood-retina barrier neovascularization. Keywords: Angiopoietins; Blood-retina barrier; Diabetic retinopathy; Endothelial cells; Macular edema; Pericytes; Retinal neovascularization; Vascular factors

Language: Английский

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The blood–retina barrier in health and disease

FEBS Journal, Journal Year: 2021, Volume and Issue: 290(4), P. 878 - 891

Published: Dec. 19, 2021

The blood-retina barrier (BRB) is the term used to define properties of retinal capillaries and pigment epithelium (RPE), which separate systemic circulation from retina. More specifically, inner (iBRB) describe endothelial cells that line microvasculature retina, while outer (oBRB) refers RPE fenestrated choriocapillaris BRB not a fixed structure; rather, it dynamic, with its components making unique contributions function structural integrity, therefore For example, tight junction (TJ) proteins between are key molecular structures in maintenance iBRB, other cell types surrounding also important. In fact, this overall structure termed neurovascular unit (NVU). integrity crucial 'dry', tightly regulated microenvironment through regulation transcellular paracellular transport. Specifically, breakdown TJs can result oedema formation, hallmark feature many diseases. Here, we will oBRB briefly, more in-depth focus on iBRB health diseased states. Finally, contribution pathophysiology age-related macular degeneration (AMD), diabetic retinopathy (DR) rarer diseases be discussed.

Language: Английский

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Photoreceptor cells and RPE contribute to the development of diabetic retinopathy

Progress in Retinal and Eye Research, Journal Year: 2020, Volume and Issue: 83, P. 100919 - 100919

Published: Nov. 12, 2020

Language: Английский

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Diabetic Macular Edema: Current Understanding, Molecular Mechanisms and Therapeutic Implications

Cells, Journal Year: 2022, Volume and Issue: 11(21), P. 3362 - 3362

Published: Oct. 25, 2022

Diabetic retinopathy (DR), with increasing incidence, is the major cause of vision loss and blindness worldwide in working-age adults. macular edema (DME) remains main impairment diabetic patients, its pathogenesis still not completely elucidated. Vascular endothelial growth factor (VEGF) plays a pivotal role DR DME. Currently, intravitreal injection anti-VEGF agents as first-line therapy DME treatment due to superior anatomic functional outcomes. However, some patients do respond satisfactorily injections. More than 30% exist persistent even after regular for at least 4 injections within 24 weeks, suggesting other pathogenic factors, beyond VEGF, might contribute Recent advances showed nearly all retinal cells are involved DME, including breakdown blood-retinal barrier (BRB), drainage dysfunction Müller glia pigment epithelium (RPE), involvement inflammation, oxidative stress, neurodegeneration, complicating The profound understanding changes proteomics metabolomics helps improve elucidation leads identification novel targets, biomarkers potential therapeutic strategies treatment. present review aimed summarize current molecular mechanisms, metabolomics, thus propose recommendations personalized

Language: Английский

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KESTREL and KITE: 52-Week Results From Two Phase III Pivotal Trials of Brolucizumab for Diabetic Macular Edema

American Journal of Ophthalmology, Journal Year: 2022, Volume and Issue: 238, P. 157 - 172

Published: Jan. 14, 2022

PurposeTo compare the efficacy and safety of brolucizumab with aflibercept in patients diabetic macular edema (DME).DesignDouble-masked, 100-week, multicenter, active-controlled, randomized trials.MethodsSubjects were 1:1:1 to 3 mg/6 mg or 2 KESTREL (n = 566) 1:1 6 KITE 360). Brolucizumab groups received 5 loading doses every weeks (q6w) followed by 12-week (q12w) dosing, optional adjustment 8 (q8w) if disease activity was identified at predefined assessment visits; 4 (q4w) fixed q8w dosing. The primary endpoint best-corrected visual acuity (BCVA) change from baseline Week 52; secondary endpoints included proportion subjects maintained on q12w Diabetic Retinopathy Severity Scale score, anatomical outcomes.ResultsAt 52, noninferior (NI margin letters) mean BCVA (KESTREL: +9.2 letters vs +10.5 letters; KITE: +10.6 +9.4 P < .001), more achieved central subfield thickness (CSFT) <280 µm, fewer had persisting subretinal and/or intraretinal fluid aflibercept, than half dosing after loading. In KITE, showed superior improvements CSFT over 40 52 (P .001). incidence ocular serious adverse events 3.7% (brolucizumab mg), 1.1% 2.1% (aflibercept) KESTREL; 2.2% mg) 1.7% KITE.ConclusionBrolucizumab robust gains an overall favorable benefit/risk profile DME. To (DME). Double-masked, trials. Subjects outcomes. At KITE.

Language: Английский

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VEGF-targeting drugs for the treatment of retinal neovascularization in diabetic retinopathy

Annals of Medicine, Journal Year: 2022, Volume and Issue: 54(1), P. 1089 - 1111

Published: April 22, 2022

Diabetic retinopathy (DR) is the most common microangiopathic complication of diabetes mellitus, representing a major cause visual impairment in developed countries. Proliferative DR (PDR) represents last stage this extremely complex retinal disease, characterized by development neovascularization induced abnormal production and release vascular endothelial growth factor (VEGF). The term VEGF includes different isoforms; VEGF-A one important pathogenic factors DR. Anti-VEGF intravitreal therapies radically changed outcome DR, due to combined anti-angiogenic anti-edematous activities. Nowadays, several anti-VEGF molecules exist, pharmacological features duration. With respect PDR, although treatments represented fundamental step forward management dramatic complication, big debate present literature regarding role as substitute panretinal photocoagulation or if these two approaches may be used combination. In review, we provided an update on isoforms their pathogenesis, current emerging new drugs, strategies PDR. There overall agreement relative advantage anti-VEGF, especially looking at PDR patients requiring vitrectomy, with laser. Based data, laser might avoided when perfectly planned therapeutic strategy can adopted. Conversely, treatment have for those unable guarantee enough compliance injections.Key messagesVEGF increased production, stimulated hypoperfusion ischaemia, neovascular onset diabetic stages progression.Nowadays, are available clinical practice other currently under investigation. Each molecule targets interact multiple biochemical pathways within eye.All data agreed considering first line choice retinopathy. Laser selected advanced cases schemes.

Language: Английский

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