Increased vitreal levels of interleukin-10 in diabetic retinopathy: a Meta-analysis

Tan, Wei; Zou, Jingling; Jiang, Bing; Zhou, Youwen

doi:10.18240/ijo.2020.09.21

Cited by 7 publications

(7 citation statements)

References 36 publications

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“…IL-10 (cytokine synthesis inhibitory factor), an anti-inflammatory cytokine, has been shown to be elevated, decreased, and also unchanged in the vitreous in PDR [24,40,43,113,120,[131][132][133]138,143,148]. The reason for this is not entirely clear but may be partially due to varying sampling methods and patient co-morbidities that could alter the immune system [133].…”

Section: Interleukinsmentioning

confidence: 99%

“…This suggests that IL-10 levels are not necessarily higher to counter-effect the pro-inflammatory response. Tan et al conducted a meta-analysis with inclusion of eleven studies showing increased IL-10 levels in the vitreous rising to significance but not in plasma or serum [148]. Due to the uncertain meaning of IL-10 levels at this time, this area requires further research.…”

Section: Interleukinsmentioning

confidence: 99%

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The Vitreous Ecosystem in Diabetic Retinopathy: Insight into the Patho-Mechanisms of Disease

Iyer

Lagrew

Tillit

et al. 2021

IJMS

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Diabetic retinopathy is one of the leading causes of blindness in the world with the incidence of disease ever-increasing worldwide. The vitreous humor represents an extensive and complex interactive arena for cytokines in the diabetic eye. In recent decades, there has been significant progress in understanding this environment and its implications in disease pathophysiology. In this review, we investigate the vitreous ecosystem in diabetic retinopathy at the molecular level. Areas of concentration include: the current level of knowledge of growth factors, cytokine and chemokine mediators, and lipid-derived metabolites in the vitreous. We discuss the molecular patho-mechanisms of diabetic retinopathy based upon current vitreous research.

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Section: Interleukinsmentioning

confidence: 99%

Section: Interleukinsmentioning

confidence: 99%

The Vitreous Ecosystem in Diabetic Retinopathy: Insight into the Patho-Mechanisms of Disease

Iyer

Lagrew

Tillit

et al. 2021

IJMS

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“…In this study, we found that FVMs tended to be closer to complete GMT after IVR therapy. Regarding the underlying mechanism, the promotion of gliosis of activated glial cells into fibrosis is induced by cytokines or profibrotic factors in the microenvironment [44][45] . Anti-VEGF agents cause structural protein abnormalities in cultured Müller cells, with decreased levels of GFAP and vimentin, probably due to the VEGF family receptors expressed in Müller cells [46][47] .…”

Section: Discussionmentioning

confidence: 99%

Effect of intravitreal ranibizumab on fibrovascular membranes in patients with proliferative diabetic retinopathy

Liang¹,

Li²,

Yang³

et al. 2022

Int J Ophthalmol

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AIM: To assess the effects of intravitreal ranibizumab (IVR) on angiogenesis and glial activity of the fibrovascular membrane (FVM) in patients with proliferative diabetic retinopathy (PDR). METHODS: Forty-two eyes from 42 patients with PDR requiring vitrectomy were included and divided into two groups: control group (n=16) did not receive IVR, while IVR group (n=26) underwent IVR 5d before vitrectomy. FVM specimens were collected by the same surgeon during the interventions. Histopathological morphology was examined by hematoxylin-eosin (H-E) staining and cell densities in the FVM was assessed. Microvessels were outlined by immunohistochemical staining of CD31 and microvessel density (MVD) assessed as an index of FVM angiogenesis. Dual-color immunofluorescence staining, and confocal microscopy was used to detect co-localization and relative expression levels of glial fibrillary acidic protein (GFAP) and α-smooth muscle actin (α-SMA) as markers of glial-mesenchymal transition (GMT). The GMT index (GI; ratio of relative GFAP/α-SMA expression) was used to semi-quantify the degree of GMT or glial activity of FVMs. RESULTS: H-E staining showed similar vascularization in both groups, with microvessels and scattered stromal cells in the matrix. Infiltrated cell densities did not differ significantly between the two groups (P>0.05). The MVD of the IVR group (130.62±15.46/mm2) was significantly lower than that of the controls (142.25±19.16/mm2, P<0.05). In both groups, all sections were strongly immunostained for GFAP and α-SMA. The Pearson's correlation coefficients (PCC) of intensity of automated pixel count of two markers indicated GFAP and α-SMA co-stained well and GMT participated in the remolding of FVMs in PDR. The mean relative GFAP expression in the IVR group was significantly lower, whereas that of α-SMA was significantly higher than in controls (P<0.05). GI in the IVR group (1.10±0.10) was significantly lower than in the controls (1.21±0.12, P<0.05). CONCLUSION: IVR can reduce angiogenesis, glial activity of FVM and promote glial-fibrotic transformation by reducing MVD and promoting GMT but does not decrease the cell density in patients with PDR.

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Section: Discussionmentioning

confidence: 99%

“…A meta-analysis of eleven studies recently showed significantly increased levels of the anti-inflammatory cytokine IL-10 in the vitreous humor of DR patients (86). Moreover, IL-10 levels were higher in patients with proliferative DR compared to patients with non-proliferative DR (86). While our data show no contribution of Müller cells to elevated IL-10 secretion upon stimulation with the tested cytokines, IL-10 induced proteins associated with tissue development, cell adhesion, and angiogenesis in MIO-M1 cells, namely Corneodesmosin (CDSN), LIF, PTN, and various collagens, to name a few.…”

Section: Discussionmentioning

confidence: 99%

Proteomic phenotyping of stimulated Müller cells uncovers profound pro-inflammatory signaling and antigen-presenting capacity

Schmalen

Lorenz

Grosche

et al. 2021

Preprint

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Mueller cells are the main macroglial cells of the retina exerting a wealth of functions to maintain retinal homoeostasis. Upon pathological changes in the retina, they become gliotic with both protective and detrimental consequences. Accumulating data also provide evidence for a pivotal role of Mueller cells in the pathogenesis of diabetic retinopathy (DR). While microglial cells, the resident immune cells of the retina are considered as main players in inflammatory processes associated with DR, the implication of activated Mueller cells in chronic retinal inflammation remains to be elucidated. In order to assess the signaling capacity of Mueller cells and their role in retinal inflammation, we performed in-depth proteomic analysis of Mueller cell proteomes and secretomes after stimulation with INFγ, TNFα, IL-4, IL-6, IL-10, TGFβ1, TGFβ2 and TGFβ3. We used both, primary porcine Mueller cells and the human Mueller cell line MIO-M1 for our hypothesis generating approach. Our results point towards an intense signaling capacity of Mueller cells, which reacted in a highly discriminating manner upon treatment with different cytokines. Stimulation of Mueller cells results in a primarily pro-inflammatory phenotype with secretion of cytokines and components of the complement system. Furthermore, we observed evidence for mitochondrial dysfunction, implying oxidative stress after treatment with the various cytokines. Finally, both MIO-M1 cells and primary porcine Mueller cells showed several characteristics of atypical antigen-presenting cells, as they are capable of inducing MHC class I and MHC class II with co-stimulatory molecules. In line with this, they express proteins associated with formation and maturation of phagosomes. Thus, our findings underline the importance of Mueller cell signaling in the inflamed retina, indicating an active role in chronic retinal inflammation underlying the pathogenesis of diabetic retinopathy.

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Increased vitreal levels of interleukin-10 in diabetic retinopathy: a Meta-analysis

Cited by 7 publications

References 36 publications

The Vitreous Ecosystem in Diabetic Retinopathy: Insight into the Patho-Mechanisms of Disease

The Vitreous Ecosystem in Diabetic Retinopathy: Insight into the Patho-Mechanisms of Disease

Effect of intravitreal ranibizumab on fibrovascular membranes in patients with proliferative diabetic retinopathy

Proteomic phenotyping of stimulated Müller cells uncovers profound pro-inflammatory signaling and antigen-presenting capacity

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