Redoxisome and diabetic retinopathy: Pathophysiology and therapeutic interventions

Sharma, Isha; Yadav, Karan Singh; Mugale, Madhav Nilakanth

doi:10.1016/j.phrs.2022.106292

Cited by 25 publications

(10 citation statements)

References 128 publications

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“…It promotes both innate and acquired immune responses to defend against infection and maintain homeostasis [ 10 ]. Nod-like receptor (NLR) family pyrin domain-containing 3 (NLRP3) is a key factor in inflammasome activation and has been reported to be involved in DR progression [ 11 , 12 ]. In an oxygen and glucose deprivation/reoxygenation in vitro model, NLRP3 activation was detected and inflammasome inactivation promoted RGC survival [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

HDAC3 Inhibition Alleviates High-Glucose-Induced Retinal Ganglion Cell Death through Inhibiting Inflammasome Activation

Tang

Liu

et al. 2022

BioMed Research International

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Purpose. The exact effects of histone deacetylase 3 (HDAC3) inhibition in DR related retinal ganglion cells (RGCs) death remained unclear. This study is aimed at detecting the influence of HDAC3 on the high-glucose-induced retinal ganglion cell death. Methods. The retinal HDAC3 expression in DR of different time points was analyzed by immunohistochemical assay and western blot. Besides, the expression of HDAC3 and both retinal thickness and RGC loss were analyzed. The effects of HDAC3 inhibitor on cell viability, oxidative stress, and apoptosis in high-glucose- (HG-) treated RGCs were analyzed. Both inflammatory and antioxidative factors were detected by ELISA. Results. Advanced effects of HDAC3 inhibition on the expression of NLRP3 inflammasome were detected using western blots. High HDAC3 expression was detected only in the late DR mice (4 months of diabetes duration) but not early DR mice (2 months of diabetes duration). The immunohistochemical assay showed that HDAC3 expression was correlated with both retinal thickness and RCG contents. HDAC3 inhibitor significantly protected the HG-treated RGCs from damaged cell viability, severe apoptosis, and oxidative stress. Advanced pathway analyses showed that HDAC3 inhibition inactivated NLRP3 inflammasome and thus alleviated retinal inflammation. Conclusion. In conclusion, HDAC3 was involved in RGC loss and thus promoted the progression of neurodegeneration of DR. Besides, HDAC3 inhibitor demonstrated protective effects in neurodegeneration in DR through downregulation of NLRP3 activity. The effects of HDAC3 inhibitor in DR management should be confirmed in clinical trials.

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Section: Introductionmentioning

confidence: 99%

HDAC3 Inhibition Alleviates High-Glucose-Induced Retinal Ganglion Cell Death through Inhibiting Inflammasome Activation

Tang

Liu

et al. 2022

BioMed Research International

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“…Txnip plays a critical role in modulating oxidative stress and inflammatory responses within cells (36)(37)(38)(39)(40). Txnip directly interacts with thioredoxin, a major antioxidant protein, inhibiting its function and expression, thereby increasing intracellular oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

Salvianolic Acid a Attenuates Angiotensin Ii-Induced Cardiac Fibrosis Through Regulating the Txnip Signaling Pathway

Ye,

Wang,

et al. 2024

Shock

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Cardiac fibrosis, characterized by excessive collagen accumulation in heart tissues, poses a significant clinical challenge in various heart diseases and complications. Although salvianolic acid A (Sal A) from Danshen (Salvia miltiorrhiza) has shown promise in the treatment of ischemic heart disease, myocardial infarction, and atherosclerosis, its effects on cardiac fibrosis remain unexplored. Our study investigated the efficacy of Sal A in reducing cardiac fibrosis and elucidated its underlying molecular mechanisms. We observed that Sal A demonstrated significant cardioprotective effects against Angiotensin II (Ang II)-induced cardiac remodeling and fibrosis, showing a dose-dependent reduction in fibrosis in mice and suppression of cardiac fibroblast proliferation and fibrotic protein expression in vitro. RNA sequencing revealed that Sal A counteracted Ang II-induced upregulation of Txnip, and subsequent experiments indicated that it acts through the inflammasome and ROS pathways. These findings establish the anti-fibrotic effects of Sal A, notably attenuated by Txnip overexpression, and highlight its significant role in modulating inflammation and oxidative stress pathways. This underscores the importance of further research on Sal A and similar compounds, especially regarding their effects on inflammation and oxidative stress, which are key factors in various cardiovascular diseases.

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“…Thus, in addition to glucose control, which was a determining factor, we found that SBP and smoking habit were probable risk factors. A review by Sharma et al [14] reported that the main pathophysiological changes in DR caused by chronic hyperglycemia included the following: (1) local ischemia and (2) basement membrane dysfunction and thickening and pericyte depletion. The major metabolic abnormalities induced by hyperglycemia involve increased glucose ux through the activation of the polyol, hexosamine, protein kinase C, and angiotensin II pathways and the accumulation of advanced glycation end-products, contributing to an imbalance in cellular redox homeostasis.…”

Section: Discussionmentioning

confidence: 99%

Associated Factors of Diabetic Retinopathy by Artificial Intelligence Evaluation of Fundus Images in Japan

Komatsu,

Sano,

Fukai

et al. 2023

Preprint

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This cross-sectional study aimed to investigate the promoting and inhibitory factors of diabetic retinopathy (DR) according to diabetes mellitus (DM) stage using standardized evaluation of fundus images by artificial intelligence (AI). A total of 30,167 participants underwent blood and fundus examinations at a health screening facility in Japan (2015–2016). Fundus photographs were screened by the AI software, RetCAD and DR scores (DRSs) were quantified. The presence of DR was determined by setting two cut-off values prioritizing sensitivity or specificity. DM was defined as four stages (no DM: DM0; advanced DM: DM3) based on treatment history and hemoglobin A1c (HbA1c) levels. Associated factors of DR were identified using logistic regression analysis. For cutoff values, multivariate analysis revealed age, sex, systolic blood pressure (SBP), smoking, urinary protein, and HbA1c level as positively associated with the risk of DR among all DM stages. In addition to glycemic control, SBP and Fib-4 might act as promoting factors for DR at all or an earlier DM stage. T-Bil, cholinesterase, and T-cho level might be protective factors at an advanced DM stage.

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Redoxisome and diabetic retinopathy: Pathophysiology and therapeutic interventions

Cited by 25 publications

References 128 publications

HDAC3 Inhibition Alleviates High-Glucose-Induced Retinal Ganglion Cell Death through Inhibiting Inflammasome Activation

HDAC3 Inhibition Alleviates High-Glucose-Induced Retinal Ganglion Cell Death through Inhibiting Inflammasome Activation

Salvianolic Acid a Attenuates Angiotensin Ii-Induced Cardiac Fibrosis Through Regulating the Txnip Signaling Pathway

Associated Factors of Diabetic Retinopathy by Artificial Intelligence Evaluation of Fundus Images in Japan

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