NOD-like Receptors in the Eye: Uncovering Its Role in Diabetic Retinopathy

Lim, Robert W.; Wieser, Margaret E.; Ganga, Rama; Barathi, Veluchamy A; Lakshminarayanan, Rajamani; Mohan, Rajiv R.; Hainsworth, Dean P.; Chaurasia, Shyam S.

doi:10.3390/ijms21030899

Cited by 47 publications

(36 citation statements)

References 196 publications

(242 reference statements)

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“…Retinal microvessels are exposed to high glucose and hypoxic environments for a long time in DM patients, and retinal sensory nerve function damage, and the changes in microvascular structure and function will occur, leading to the onset and development of DR [24].…”

Section: Discussionmentioning

confidence: 99%

VEGF, apelin and HO-1 in diabetic patients with retinopathy: a correlation analysis

Zhu

Zhou

2020

BMC Ophthalmol

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Background: It's necessary to analyze the role of VEGF, apelin, and HO-1 in patients with type 2 diabetes (T2DM), and to evaluate its relevance to diabetic retinopathy (DR). Methods: T2DM patients who were treated in our hospital from December 1, 2018 to November 30, 2019 were included. T2DM patients were divided into non-DR (NDR) group, non-proliferative DR (NPDR) group, and proliferative DR (PDR) group. and healthy participants were selected as the control group. The value of VEGF, apelin, and HO1 in predicting PDR were analyzed by receiver operating characteristic (ROC) curve, and the relations of VEGF, apelin, HO-1 and clinical factors in PDR patients were analyzed by Pearson correlation analysis. Results: A total of 295 participants were included. The level of FPG and HbAlc in PDR group were significantly higher than that of other groups (all p < 0.05); the level of VEGF and apelin in PDR group were significantly higher than that of other groups (all p < 0.05), but the level of HO-1 in PDR group were significantly less than that of other groups(p = 0.017); the AUC of VEGF, apelin, HO-1 and combined use was 0.806(95%CI: 0.779-0.861), 0.819(95%CI: 0.765-0.878), 0.808(95%CI: 0.733-0.869) and 0.902(95%CI: 0.822-0.958) respectively, the AUC, sensitivity, specificity of the three combined use was significantly higher than that of single VEGF, apelin, HO-1 use(all p < 0.05). The cutoff values of serum VEGF, apelin, and HO-1 levels for predicting PDR were 163.85 pg/ml, 8.27 ng/ml, and 26.06 mmol/L respectively. Serum VEGF, apelin, and HO-1 in patients with PDR was related to the time course of DM, FPG and HbAlc (all p < 0.05). Conclusions: VEGF, apelin and HO-1 are related to the progress of DR, and the combined use of VEGF, apelin and HO-1 is beneficial to the diagnosis and treatment of PDR.

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Section: Discussionmentioning

confidence: 99%

VEGF, apelin and HO-1 in diabetic patients with retinopathy: a correlation analysis

Zhu

Zhou

2020

BMC Ophthalmol

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“…This would appear independent of the relatively acute effects of fenofibrate since the large rise in serum creatinine in the present case would, based on trial evidence [ 11 ], have a neutral rather than a beneficial effect on long-term renal function. The benefits of fenofibrate in preventing progression of diabetic retinopathy [ 6 , 7 ] may also be mediated through inhibition of NLRP3 inflammasome activation [ 16 ], and T1R2-T1R3 binding could have a contributory role in some patients.…”

Section: Discussionmentioning

confidence: 99%

“…If fenofibrate binds to and inhibits T1R2-T1R3, its use may have implications for the development of chronic microvascular complications. Stimulation of T1R2-T1R3 in the kidneys and retina may be deleterious through activation of the inflammasome, the cytosolic protein complexes mediating inflammatory responses, which could lead to tissue damage [ 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

Fenofibrate and Impaired Taste Perception in Type 2 Diabetes

Davis

2020

Am J Case Rep

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Patient: Female, 65-year-old Final Diagnosis: Type 2 diabetes Symptoms: Loss of sweet taste Medication: Fenofibrate Clinical Procedure: Drug challenge/dechallenge/rechallenge Specialty: Endocrinology and Metabolic Objective: Unusual clinical course Background: Although reduced sweet taste perception has been found in studies of clofibrate in healthy volunteers, this phenomenon has not been reported for the chemically related and more widely used drug fenofibrate. Case Report: A 65-year-old woman with insulin-treated type 2 diabetes was initiated on fenofibrate for worsening diabetic retinopathy. She subsequently developed a marked loss of sweet taste perception. After 3 months of fenofibrate, her glycemic control had improved and her insulin requirements had decreased, probably as a result of anorexia. Her renal function had also worsened. Dechallenge resulted in near normalization of sweet taste and restoration of her pretreatment renal function 2 weeks later. Rechallenge provoked recurrence of severely impaired sweet taste perception, which led to permanent discontinuation of fenofibrate. Conclusions: This case shows that altered sweet taste perception is a potential clinically significant adverse effect of fenofibrate therapy. There is increasing interest in the function of sweet taste receptors, which are recognized as having a broader role in cellular function and inflammation in tissues such as the kidney and retina that are relevant to type 2 diabetes and its complications.

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“…Generally, NLRs are organized in a tripartite structure: the N-terminal effector domain (pyrin (PYD) for NLRPs; caspaserecruitment domain (CARD) for NLRCs) required for signal transduction, the central NACHT domain (contains NBD) mediates self-oligomerization, and the C-terminal leucine-rich repeats (LRRs) involved in ligand detection (24,25). In most cases.…”

Section: Inflammasomesmentioning

confidence: 99%

Nuclear Receptors as Multiple Regulators of NLRP3 Inflammasome Function

Alatshan

Benkő

2021

Front. Immunol.

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Nuclear receptors are important bridges between lipid signaling molecules and transcription responses. Beside their role in several developmental and physiological processes, many of these receptors have been shown to regulate and determine the fate of immune cells, and the outcome of immune responses under physiological and pathological conditions. While NLRP3 inflammasome is assumed as key regulator for innate and adaptive immune responses, and has been associated with various pathological events, the precise impact of the nuclear receptors on the function of inflammasome is hardly investigated. A wide variety of factors and conditions have been identified as modulators of NLRP3 inflammasome activation, and at the same time, many of the nuclear receptors are known to regulate, and interact with these factors, including cellular metabolism and various signaling pathways. Nuclear receptors are in the focus of many researches, as these receptors are easy to manipulate by lipid soluble molecules. Importantly, nuclear receptors mediate regulatory mechanisms at multiple levels: not only at transcription level, but also in the cytosol via non-genomic effects. Their importance is also reflected by the numerous approved drugs that have been developed in the past decade to specifically target nuclear receptors subtypes. Researches aiming to delineate mechanisms that regulate NLRP3 inflammasome activation draw a wide range of attention due to their unquestionable importance in infectious and sterile inflammatory conditions. In this review, we provide an overview of current reports and knowledge about NLRP3 inflammasome regulation from the perspective of nuclear receptors, in order to bring new insight to the potentially therapeutic aspect in targeting NLRP3 inflammasome and NLRP3 inflammasome-associated diseases.

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NOD-like Receptors in the Eye: Uncovering Its Role in Diabetic Retinopathy

Cited by 47 publications

References 196 publications

VEGF, apelin and HO-1 in diabetic patients with retinopathy: a correlation analysis

VEGF, apelin and HO-1 in diabetic patients with retinopathy: a correlation analysis

Fenofibrate and Impaired Taste Perception in Type 2 Diabetes

Nuclear Receptors as Multiple Regulators of NLRP3 Inflammasome Function

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