Thioredoxin-interacting protein in diabetic retinal neurodegeneration: A novel potential therapeutic target for diabetic retinopathy

Liu, Chengzhi; Dong, Wenkang; Lv, Zhengshuai; Kong, Li; Ren, Xiang

doi:10.3389/fnins.2022.957667

Cited by 5 publications

(3 citation statements)

References 97 publications

(106 reference statements)

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“…Mitigating OXS was previously reported to decrease hyperglycemia-induced neuronal damage [4]. In addition, proper glutamate metabolism was found to be crucial for the maintenance of retinal health [5]. Diabetes could contribute to glutamate accumulation in the retina, which eventually leads to the hyperexcitation of N-methyl-D-aspartate receptors (NMDARs), enhancement of calcium influx and retinal neurodegeneration [6].…”

Section: Introductionmentioning

confidence: 99%

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Protective Effect of Topiramate against Diabetic Retinopathy and Computational Approach Recognizing the Role of NLRP3/IL-1β/TNF-α Signaling

Mohammad,

Eladl,

Abdelmaogood

et al. 2023

Biomedicines

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The possible impact of topiramate against diabetic retinopathy (DREN) and its molecular mechanisms in relation to the nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome has not been studied before. Thus, in the present study, we aimed to utilize a computational approach to investigate the possible protective effect of topiramate on experimental DREN and explore its impact on NLRP3/interlukin-1β signaling and brain-derived neurotrophic factor (BDNF) expression. Male albino mice were distributed to four experimental groups and assigned the following categorizations: (i) saline, (ii) diabetic, (iii) diabetic + topiramate 10 mg/kg and (iv) diabetic + topiramate 30 mg/kg. We observed shrinkage of total retinal thickness and elevation in retinal glutamate, malondialdehyde, NLRP3 and interlukin-1β but decreased glutathione (GSH) levels in the diabetic mice. Additionally, retinal ultra-structures in the diabetic group showed abnormalities and vacuolations in the pigmented epithelium, the photoreceptor segment, the outer nuclear layer, the inner nuclear layer and the ganglion cell layer (GCL). Mice treated with topiramate 10 or 30 mg/kg showed downregulation in retinal malondialdehyde, NLRP3 and interlukin-1β levels; improvements in the retinal pathologies; enhanced immunostaining for BDNF and improved ultra-structures in different retinal layers. Overall, the current results suggest topiramate as a neuroprotective agent for DREN, and future studies are warranted to further elucidate the mechanism of its protective action.

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Section: Introductionmentioning

confidence: 99%

“…At present, three drugs have been approved by the US Food and Drug Administration for DREN, namely ranibizumab, pegaptanib and aflibercept. They decrease the rate of retinal deterioration [5]. Ranibizumab and aflibercept are administered as an intravitreal injection into the eye.…”

Section: Introductionmentioning

confidence: 99%

Protective Effect of Topiramate against Diabetic Retinopathy and Computational Approach Recognizing the Role of NLRP3/IL-1β/TNF-α Signaling

Mohammad,

Eladl,

Abdelmaogood

et al. 2023

Biomedicines

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show abstract

“…Statistically, the ratio of blindness caused by DR ranged from 15-17% in developed areas [4]. Notably, it is reported that oxidative stress, apoptosis, and inflammation can promote the development of DR [5,6]. Studies in diabetic mice demonstrated that inflammatory processes aggravated the occurrence of DR by upregulating the expression of pro-inflammatory cytokine [7].…”

Section: Introductionmentioning

confidence: 99%

SRY-box transcription factor 9 modulates Müller cell gliosis in diabetic retinopathy by upregulating TXNIP transcription

Ouyang

Yuan

et al. 2023

Exp. Anim.

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Diabetic retinopathy (DR), a common complication of diabetes, involves excessive proliferation and inflammation of Muller cells and ultimately leads to vision loss and blindness. SRY-box transcription factor 9 (SOX9) has been reported to be highly expressed in Müller cells in retinal light-damaged rats, but the functional role of SOX9 in DR remains unclear. To explore this issue, the DR rat model was successfully constructed via injecting with streptozotocin (STZ, 65 mg/kg) and the retinal thicknesses and blood glucose levels were evaluated. Müller cells were treated with 25 mmol/L glucose to create a cell model in vitro. The results indicated that SOX9 expression was significantly increased in DR rat retinas and high glucose (HG)-stimulated Müller cells. HG treatment promoted the proliferation and migration capabilities of Müller cells, whereas SOX9 knockdown reversed those behaviors. Moreover, SOX9 knockdown protected against HG-induced inflammatory response, as evidenced by reduced tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6 levels in serum and decreased NLRP3 inflammasome activation. Notably, SOX9, acted as a transcription factor that positively regulated thioredoxin-interacting protein (TXNIP), a positive regulator of Müller cells gliosis under HG conditions. Dual luciferase assay demonstrated that SOX9 could enhance TXNIP expression at the transcriptional level through binding to the promoter of TXNIP. Moreover, TXNIP overexpression restored the effects caused by SOX9 silencing. In conclusion, these findings demonstrate that SOX9 may accelerate the progression of DR by promoting glial cell proliferation, metastasis, and inflammation, which involves the transcriptional regulation of TXNIP, providing new theoretical fundamentals for DR therapy.

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MicroRNA-204-5p Attenuates Oxidative Stress, Apoptosis and Inflammation by Targeting TXNIP in Diabetic Cataract

Cao,

Jiang,

et al. 2024

Biochem Genet

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Diabetic cataract (DC) is a major cause of blindness in diabetic patients and it is characterized by early onset and rapid progression. MiR-204-5p was previously identi ed as one of the top ve down-regulated miRNAs in human DC lens tissues. We aimed to determine the expression of miR-204-5p in human lens epithelial cells (HLECs) and explore its effects and mechanisms in regulating the progression of DC. The expression of miR-204-5p in the anterior capsules of DC patients and HLECs was examined by RT-qPCR. Bioinformatics tools were then used to identify the potential target of miR-204-5p. The relationship between miR-204-5p and the target gene was con rmed through a dual luciferase reporter assay. Additionally, the regulatory mechanism of oxidative stress, apoptosis, and in ammation in DC was investigated by overexpressing miR-204-5p using miR-204-5p agomir. The expression of miR-204-5p was downregulated in the anterior capsules of DC patients and HLECs. Overexpression of miR-204-5p reduced ROS levels, pro-apoptosis genes (Bid, Bax, caspase-3), and IL-1β production in HG-treated HLECs. TXNIP was the direct target of miR-204-5p by dual luciferase reporter assay. Therefore, This study demonstrated that miR-204-5p effectively reduced oxidative damage, apoptosis, and in ammation in HLECs under HG conditions by targeting TXNIP. Targeting miR-204-5p could be a promising therapeutic strategy for the potential treatment of DC.

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Thioredoxin-interacting protein in diabetic retinal neurodegeneration: A novel potential therapeutic target for diabetic retinopathy

Cited by 5 publications

References 97 publications

Protective Effect of Topiramate against Diabetic Retinopathy and Computational Approach Recognizing the Role of NLRP3/IL-1β/TNF-α Signaling

Protective Effect of Topiramate against Diabetic Retinopathy and Computational Approach Recognizing the Role of NLRP3/IL-1β/TNF-α Signaling

SRY-box transcription factor 9 modulates Müller cell gliosis in diabetic retinopathy by upregulating TXNIP transcription

MicroRNA-204-5p Attenuates Oxidative Stress, Apoptosis and Inflammation by Targeting TXNIP in Diabetic Cataract

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