Regression of Sight-Threatening Macular Edema in Type 2 Diabetes Following Treatment With the Anti–Tumor Necrosis Factor Monoclonal Antibody Infliximab

Sfikakis, Petros P.; Markomichelakis, Nikos N.; Theodossiadis, George; Grigoropoulos, Vlassis; Katsilambros, N.; Theodossiadis, Panayiotis G.

doi:10.2337/diacare.28.2.445

Cited by 87 publications

(54 citation statements)

References 15 publications

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“…TNF inhibition also reduced the effect of diabetes-enhanced leukocyte adhesion, expression of eNOS, activation of NF-kappaB and blood-retinal barrier breakdown. In addition, positive results have been obtained in humans using a TNF inhibitor to treat diabetic macular edema (134). Treatment with the TNF inhibitor etanercept in a related experimental pathology, LPS induced uveitis, significantly reduced inflammation and apoptosis in the retina (135).…”

Section: Retinopathymentioning

confidence: 92%

Diabetic complications and dysregulated innate immunity

Graves

Kayal²

2008

Front Biosci

227

188

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Diabetes mellitus is a metabolic disorder that leads to the development of a number of complications. The etiology of each diabetic complication is undoubtedly multifactorial. We will focus on one potential component that may be common in many diabetic complications, dysregulation of innate immunity associated with an increased inflammatory response. High glucose levels lead to shunting through the polyol pathway, an increase in diacylglycerol which activates protein kinase C, an increase in the release of electrons that react with oxygen molecules to form superoxides, and the non-enzymatic glycosylation of proteins that result in greater formation of advanced glycation end products. Each of these can lead to aberrant cell signalling that affects innate immunity for example, by activating the MAP kinase pathway or inducing activation of transcription factors such as NF-kappaB. This may be a common feature of several complications including periodontal disease, atherosclerosis, nephropathy, impaired healing and retinopathy. These complications are frequently associated with increased expression of inflammatory cytokines such as TNF-alpha, IL-1beta and IL-6 and enhanced generation of reactive oxygen species. Cause and effect relationship between dysregulation of key components of innate immunity and diabetic complications in many instances have been demonstrated with the use of cytokine blockers and antioxidants.

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Section: Retinopathymentioning

confidence: 92%

Diabetic complications and dysregulated innate immunity

Graves

Kayal²

2008

Front Biosci

227

188

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“…However, OCT measurements of retinal thicknesses and DR severity grading of fundus photographs showed no significant anatomical improvements with anti-TNF-α treatment. An earlier study of four patients treated with systemic Infliximab observed both functional and anatomical improvements in four of six eyes examined [155]. It should be noted that two recent studies examining intravitreal injections of anti-TNF-α therapeutics, including Infliximab and Adalimumab (Humira), in refractory DME patients found no DR.…”

Section: Additional Cytokines In Drmentioning

confidence: 98%

Angiogenic Factors and Cytokines in Diabetic Retinopathy

Abcouwer¹

2011

J Clin Cell Immunol

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Diabetic retinopathy (DR) is a sight-threatening complication of both type-1 and type-2 diabetes. The recent success of treatments inhibiting the function of vascular endothelial growth factor (VEGF) demonstrates that specific targeting of a growth factor responsible for vascular permeability and growth is an effective means of treating DRtargets involved in the control of retinal vascular function. However, additional treatment options and preventative measures are still needed and these require a greater understanding of the pathological mechanisms leading to the disturbance of retinal tissue homeostasis in DR. Although severe DR can be treated as a vascular disease, abundant data suggests that inflammation is also occurring in the diabetic retina.Thus, anti-inflammatory therapies may also be useful for treatment and prevention of DR. Herein, the evidence for altered expression of angiogenic factors and cytokines in DR is reviewed and possible mechanisms by which the expression of VEGF and cytokines may be increased in the diabetic retina are examined. In addition, the potential role for microglial activation in diabetic retinal neuroinflammation is explored.

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“…Other less specific treatments with a component of anti-TNF activity have improved experimental diabetic neuropathy in rats (Chauhan et al, 2012) and limited peripheral neuropathy progression (Sagara et al, 1996). In humans, TNF blockers reduce macular thickness and increase visual acuity in patients with severe diabetic macular edema (Sfikakis et al, 2005).…”

Section: Introduction Tmentioning

confidence: 99%