Local and Systemic Inflammatory Biomarkers of Diabetic Retinopathy: An Integrative Approach

Vujosevic, Stela; Simó, Rafael

doi:10.1167/iovs.17-21769

Cited by 130 publications

(116 citation statements)

References 93 publications

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“…First, aqueous humour is currently the most commonly used intraocular specimen for the study of retinal diseases, but vitreous fluid, as an index of primarily posterior segment pathology, should be considered the ideal sample in such cases. 14,40,41 However, aqueous sampling is less invasive than vitreous fluid sampling. Therefore, aqueous humour is considered the most appropriate biological sample for examining the intraocular biomarkers of DME.…”

Section: Discussionmentioning

confidence: 99%

“…13 Cellular events such as the increased expression of inflammatory mediators, leucostasis, and abnormal leukocyte adherence result in increased vascular permeability in the pathogenesis of DME. 14,15 It has been reported that the levels of VEGF, interleukin (IL)-6, IL-8, intercellular adhesion molecule-1 (ICAM-1), interferon gamma-induced protein-10 (IP-10), and monocyte chemoattractant protein-1 (MCP-1) are increased in DME patients compared with diabetic patients without DME. 16 However, the exact mechanisms and reasons for the response to anti-VEGF treatment in DME patients remain unclear.…”

Section: Introductionmentioning

confidence: 99%

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<p>Cytokine and Chemokine Profile Changes in Patients After Intravitreal Conbercept Injection for Diabetic Macular Edema</p>

Wei¹,

Wan²,

Hu³

et al. 2019

DDDT

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These authors contributed equally to this workPurpose: This study aimed to investigate the concentrations of cytokines and chemokines in diabetic macular edema (DME) eyes before and during therapy with the intravitreal injection of conbercept (IVC) and to identify associations with disease activity. Methods: The Bio-Plex ® 200 System and the Bio-PlexTM Human Cytokine Standard 27-Plex, Group I (Bio-Rad, Hercules, California, USA) were used to detect cytokine levels in aqueous humour. Experimental aqueous humour samples were collected from 18 patients with DME at the same time that IVC was performed at baseline and at 1 month. Control aqueous humour samples were collected from 16 patients undergoing cataract surgery. Results: Significantly higher concentrations of vascular endothelial growth factor (VEGF), interleukin 6 (IL-6), IL-8, eotaxin, granulocyte colony stimulating factor (G-CSF), interferon gamma-induced protein 10 (IP-10), and monocyte chemoattractant protein-1 (MCP-1) were found in the aqueous humour of DME patients than cataract patients. One month after IVC, the intraocular concentrations of VEGF were significantly lower in the eyes of DME patients than at baseline. No other cytokines were significantly altered by conbercept therapy. Bestcorrected visual acuity (BCVA) slightly improved following IVC compared with that at baseline, although this difference was not significant, and central macular thickness (CMT) significantly decreased 1 month after IVC treatment. Conclusion: Angiogenic, inflammatory and growth factors are involved in the development of DME. With the exception of VEGF, IVC did not cause significant differences in any inflammatory cytokines or growth factors in DME patients. CMT is related to VEGF levels in aqueous humour.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

<p>Cytokine and Chemokine Profile Changes in Patients After Intravitreal Conbercept Injection for Diabetic Macular Edema</p>

Wei¹,

Wan²,

Hu³

et al. 2019

DDDT

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“…The main contributor to DME development has been thought to be the intraocular production of proinﬂam matory cytokines such as IL-6, IL-8, TNF-α, IL-1β, VEGF, pigment epithelium-derived factor, ICAM-1, and monocyte chemotactic protein (MCP-1) [9, 10, 24, 25]. There are very few data with regard to the altered levels of inflammatory mediators in peripheral blood of DME patients, in contrast to those mediators in intraocular blood [9, 11].…”

Section: Discussionmentioning

confidence: 99%

A Novel Biomarker in Diabetic Macular Edema with Serous Retinal Detachment: Serum Chitinase-3-Like Protein 1

Kaya

İdıman

et al. 2018

Ophthalmologica

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Purpose: To determine whether serum chitinase-3-like protein 1 (CHI3L1) and interleukin-6 (IL-6) levels correlate with serous retinal detachment (SRD) in diabetic macular edema (DME) using spectral-domain optical coherence tomography (SD-OCT). Methods: In this cross-sectional case-control study, 394 patients (treatment-naive DME patients, n = 218; diabetic patients without DME, n = 96; nondiabetic controls, n = 80) were included in the study. Eyes were classiﬁed according to SD-OCT features of DME: SRD, cystoid macular edema (CMO), and diffuse retinal thickness (DRT). Serum concentrations of CHI3L1 and IL-6 were analyzed using enzyme-linked immunosorbent assay. Results: Serum CHI3L1 and IL-6 levels were significantly higher in DME with SRD compared to patients with CMO and DRT (p < 0.001 for all groups). Multivariate regression analysis showed that CHI3L1 and IL-6 had a stronger influence on the presence of SRD in DME (r = 1.162, p = 0.026, and r = 1.242, p = 0.016, respectively). Serum concentration of CHI3L1 was significantly correlated with that of IL-6 (r = 0.386, p = 0.0015). Conclusions: Our data suggest that serum concentrations of CHI3L1 and IL-6 are involved in the process of SRD in DME. CHI3L1 can be investigated further as a new diagnostic biomarker for DME with SRD.

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“…The generated reparative enzymes, formerly termed "heat shock proteins" that resulted from retinal pigment epithelium non-lethal laser heating that have thus far been measured include reductions in thiobarbituric acid reactive substances (TBARS), increased glutathione (GSH) and superoxide dismutase 1 (SOD1) as well as a reduction in cytochrome c, caspase 3 expression and activity along with cleaved caspase 9, and increased Beclin 1, p62, and LC3b (131). Reductions in markers of inflammation have also been documented in human diabetic retinopathy (132,133), and micropulsed laser treatment has been demonstrated to improved early forms of macular edema with significant improvement in vision and without evidence of laser injury (133)(134)(135). When the macular edema is more severe, however, similar to the studies of intravitreal anti-VEGF injections, the studies of micropulsed laser demonstrate only minimal improvement in the edema and in vision (presumably because of the already established, irreversible neurodegeneration) (11,133).…”

Section: Treatment/prevention Of Neurodegenerationmentioning

confidence: 99%

Diabetic Retinopathy–An Underdiagnosed and Undertreated Inflammatory, Neuro-Vascular Complication of Diabetes

Sinclair

Schwartz

2019

Front. Endocrinol.

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Diabetes mellitus is a world-wide epidemic and diabetic retinopathy, a devastating, vision-threatening condition, is one of the most common diabetes-specific complications. Diabetic retinopathy is now recognized to be an inflammatory, neuro-vascular complication with neuronal injury/dysfunction preceding clinical microvascular damage. Importantly, the same pathophysiologic mechanisms that damage the pancreatic β-cell (e.g., inflammation, epigenetic changes, insulin resistance, fuel excess, and abnormal metabolic environment), also lead to cell and tissue damage causing organ dysfunction, elevating the risk of all complications, including diabetic retinopathy. Viewing diabetic retinopathy within the context whereby diabetes and all its complications arise from common pathophysiologic factors allows for the consideration of a wider array of potential ocular as well as systemic treatments for this common and devastating complication. Moreover, it also raises the importance of the need for methods that will provide more timely detection and prediction of the course in order to address early damage to the neurovascular unit prior to the clinical observation of microangiopathy. Currently, treatment success is limited as it is often initiated far too late and after significant neurodegeneration has occurred. This forward-thinking approach of earlier detection and treatment with a wider array of possible therapies broadens the physician's armamentarium and increases the opportunity for prevention and early treatment of diabetic retinopathy with preservation of good vision, as well the prevention of similar destructive processes occurring among other organs.

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Local and Systemic Inflammatory Biomarkers of Diabetic Retinopathy: An Integrative Approach

Cited by 130 publications

References 93 publications

<p>Cytokine and Chemokine Profile Changes in Patients After Intravitreal Conbercept Injection for Diabetic Macular Edema</p>

<p>Cytokine and Chemokine Profile Changes in Patients After Intravitreal Conbercept Injection for Diabetic Macular Edema</p>

A Novel Biomarker in Diabetic Macular Edema with Serous Retinal Detachment: Serum Chitinase-3-Like Protein 1

Diabetic Retinopathy–An Underdiagnosed and Undertreated Inflammatory, Neuro-Vascular Complication of Diabetes

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