Changes in TL1A levels and associated cytokines during pathogenesis of diabetic retinopathy

Zhang, Zhu‐Hong; Chen, Qingzhong; Jiang, Feng; Townsend, Todd A.; Mao, Chunjie; You, Caiyun; Yang, Wenhui; Sun, Zhibin; Jin, Yu; Yan, Hua

doi:10.3892/mmr.2016.6048

Cited by 10 publications

(9 citation statements)

References 33 publications

(57 reference statements)

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“…Furthermore, a positive correlation was found between TL1A and the pro‐inflammatory cytokines, MCP‐1 and MIP‐1α, in the ocular fluid of PDR patients. These results are in line with our previous finding that diabetes can upregulate the expression of TL1A and inflammatory cytokines such as VEGF, TNF‐α and IL‐1β in the retinas of diabetic rats 38 . Abu El et al 39 showed that TL1A expression was significantly increased in vitreous fluids from PDR patients and in the retinas of diabetic rats, which are likely to contribute to the persistent inflammatory process.…”

Section: Discussionsupporting

confidence: 92%

Intraocular tumour necrosis factor ligand related molecule 1 A links disease progression of proliferative diabetic retinopathy after primary vitrectomy

Xie

Wang

et al. 2020

Clin Exp Pharma Physio

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Tumour necrosis factor ligand related molecule 1 A (TL1A), a member of tumour necrosis factor superfamily, has been identified as a crucial regulator for vascular homeostasis and inflammation. However, the function of TL1A in diabetic retinopathy (DR) is largely unknown. This study aims to examine levels of TL1A in serum and intraocular fluid in patients with proliferative diabetic retinopathy (PDR), and to explore the correlation of intraocular TL1A with the prognosis of PDR progression after primary vitrectomy. Seventy‐five patients (75 eyes) with PDR who underwent pars plana vitrectomy (PPV) and 19 patients (19 eyes) who received vitrectomy for idiopathic macular holes (IMH) as non‐diabetic control group were enrolled in this prospective study. Serum, aqueous and vitreous fluid samples were collected during cataract and PPV surgery. Protein expressions of TL1A as well as other angiogenic and inflammatory cytokines in serum and intraocular fluid were measured. Correlations of intraocular TL1A concentrations with inflammatory cytokines were analyzed. We found both aqueous and vitreous TL1A levels were significantly higher in the PDR group than in control group (Paqueous = 0.026; Pvitreous <0.001). Angiogenic and inflammatory cytokines such as VEGF, IL‐6, IL‐8, MCP‐1, MIP‐1α, and MIP‐1β were significantly higher in intraocular fluid in PDR group than in controls, which MCP‐1 and MIP‐1α showed positive correlation with intraocular TL1A levels. There is no significant difference in the levels of serum TL1A as well as other inflammatory cytokines between PDR patients and controls. Intraocular levels of TL1A were significantly lower in PDR progression group than in the stable group (Paqueous <0.001; Pvitreous <0.001). Multivariate logistic regression analyses revealed that lower levels of intraocular TL1A was an important risk factor for predicting PDR progression after primary PPV (ORaqueous = 0.717, Paqueous = 0.001; ORvitreous = 0.684; Pvitreous = 0.002). In conclusion, TL1A and multiple inflammatory cytokines were highly enriched in the intraocular fluid of PDR patients compared with the controls. Lower levels of intraocular TL1A were associated with development of PDR complications after primary PPV and might be used as prognostic factor in predicting the vitrectomy outcome in PDR patients.

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Section: Discussionsupporting

confidence: 92%

Intraocular tumour necrosis factor ligand related molecule 1 A links disease progression of proliferative diabetic retinopathy after primary vitrectomy

Xie

Wang

et al. 2020

Clin Exp Pharma Physio

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“…VEGF is the most potent vasoactive factor, the normal expression of which is necessary for maintaining the structural and functional homeostasis of the retinal cells, but whose overexpression could lead to retinal angiogenesis in the effects of pathological factors such as hypoxia and hyperglycemia [6]. In diabetic rat models, retinal angiogenesis occurred at about six months, and at the same time, VEGF was significantly highly expressed in both retinal tissue and serum [7]; and the change dynamics of VEGF expression in serum were remarkably similar to those in the retina and vitreous with the progression of DR [8]. Furthermore, clinical studies showed that vitreous and circulating VEGF in the serum or plasma was increased markedly in patients with PDR, and there was a significantly positive correlation between them [9, 10].…”

Section: Introductionmentioning

confidence: 99%

Serum Vascular Endothelial Growth Factor Levels Correlate with Severity of Retinopathy in Diabetic Patients: A Systematic Review and Meta-Analysis

Zhou

Sun

et al. 2019

Disease Markers

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Background. Investigations regarding serum and plasma vascular endothelial growth factor (VEGF) levels in patients with diabetic retinopathy (DR) are conflicting. This meta-analysis is aimed at determining whether serum and plasma VEGF levels are associated with DR and its severity in diabetic patients. Methods. PubMed and EMBASE were used to search for published studies, and serum and plasma VEGF levels were compared among DR, nonproliferative diabetic retinopathy (NPDR), proliferative diabetic retinopathy (PDR), and nondiabetic retinopathy (NDR) patients. Standardized mean differences (SMD) and 95% confidence interval (CI) were pooled using a random effects model. Results. A total of 29 studies comprising 1805 DR (or NPDR or PDR) patients and 1699 NDR patients were included. ELISA was used to evaluate serum or plasma VEGF levels in all except for two studies included in this meta-analysis. Overall, serum VEGF levels were significantly higher in DR patients (SMD: 0.74, 95% CI: 0.44-1.03) than those in NDR patients, while plasma VEGF levels were not in the comparison (SMD: 0.40, 95% CI: −0.13-0.92). Similarly, NPDR (SMD: 0.51, 95% CI: 0.22-0.80) and PDR (SMD: 1.32, 95% CI: 0.79-1.85) patients had higher serum VEGF levels compared with NDR patients, but the difference was not significant in plasma samples (SMD: 0.24, 95% CI: −0.47-0.95; SMD: 0.37, 95% CI: −0.30-1.05). In addition, serum VEGF levels were higher in PDR patients than those in NPDR patients (SMD: 0.87, 95% CI: 0.41-1.33), but plasma VEGF levels were not (SMD: −0.00, 95% CI: −0.31-0.31). The subgroup and metaregression analysis revealed that the study location, study design, and publication year of a study have certain influence on heterogeneity between studies in serum or plasma samples. Conclusions. VEGF levels in the serum instead of those in the plasma correlate to the presence and severity of DR in diabetic patients. Further large-scale studies are required to confirm these findings.

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“…Death receptor 3 (DR3) (TNFRSF25), a member of TNFR superfamily expressed primarily on lymphocytes and innate lymphoid cells (ILCs), is a receptor for the cytokine TL1A (TNFSF15) secreted by dendritic cells, monocytes, macrophages, plasma cells, synovial fibroblasts, and endothelial cells ( 4 – 12 ). Preclinical and clinical studies have clearly shown a fundamental role for the TL1A/DR3 cytokine/receptor pair in the pathogenesis of inflammatory diseases, including rheumatoid arthritis ( 13 – 15 ), diabetic retinopathy ( 16 ), pulmonary sarcoidosis ( 17 ), asthma ( 10 , 18 ), and, especially, IBD ( 19 ). Precisely, TL1A and DR3 expression is significantly increased, in an inflammation-specific manner, in both serum and inflamed tissues in IBD patients and in murine experimental ileitis ( 19 ).…”

Section: Introductionmentioning

confidence: 99%

Death Receptor 3 Signaling Controls the Balance between Regulatory and Effector Lymphocytes in SAMP1/YitFc Mice with Crohn’s Disease-Like Ileitis

Buttó

Buela

et al. 2018

Front. Immunol.

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Death receptor 3 (DR3), a member of the tumor necrosis factor receptor (TNFR) superfamily, has been implicated in regulating T-helper type-1 (TH1), type-2 (TH2), and type-17 (TH17) responses as well as regulatory T cell (Treg) and innate lymphoid cell (ILC) functions during immune-mediated diseases. However, the role of DR3 in controlling lymphocyte functions in inflammatory bowel disease (IBD) is not fully understood. Recent studies have shown that activation of DR3 signaling modulates Treg expansion suggesting that stimulation of DR3 represents a potential therapeutic target in human inflammatory diseases, including Crohn’s disease (CD). In this study, we tested a specific DR3 agonistic antibody (4C12) in SAMP1/YitFc (SAMP) mice with CD-like ileitis. Interestingly, treatment with 4C12 prior to disease manifestation markedly worsened the severity of ileitis in SAMP mice despite an increase in FoxP3+ lymphocytes in mesenteric lymph node (MLN) and small-intestinal lamina propria (LP) cells. Disease exacerbation was dominated by overproduction of both TH1 and TH2 cytokines and associated with expansion of dysfunctional CD25−FoxP3+ and ILC group 1 (ILC1) cells. These effects were accompanied by a reduction in CD25+FoxP3+ and ILC group 3 (ILC3) cells. By comparison, genetic deletion of DR3 effectively reversed the inflammatory phenotype in SAMP mice by promoting the expansion of CD25+FoxP3+ over CD25−FoxP3+ cells and the production of IL-10 protein. Collectively, our data demonstrate that DR3 signaling modulates a multicellular network, encompassing Tregs, T effectors, and ILCs, governing disease development and progression in SAMP mice with CD-like ileitis. Manipulating DR3 signaling toward the restoration of the balance between protective and inflammatory lymphocytes may represent a novel and targeted therapeutic modality for patients with CD.

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Changes in TL1A levels and associated cytokines during pathogenesis of diabetic retinopathy

Cited by 10 publications

References 33 publications

Intraocular tumour necrosis factor ligand related molecule 1 A links disease progression of proliferative diabetic retinopathy after primary vitrectomy

Intraocular tumour necrosis factor ligand related molecule 1 A links disease progression of proliferative diabetic retinopathy after primary vitrectomy

Serum Vascular Endothelial Growth Factor Levels Correlate with Severity of Retinopathy in Diabetic Patients: A Systematic Review and Meta-Analysis

Death Receptor 3 Signaling Controls the Balance between Regulatory and Effector Lymphocytes in SAMP1/YitFc Mice with Crohn’s Disease-Like Ileitis

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