Sulforaphane delays diabetes-induced retinal photoreceptor cell degeneration

Lv, Jinjuan; Bao, Shuyin; Liu, Tianhe; Wei, Limin; Wang, Dongming; Ye, Weikang; Wang, Na; Song, Shiyu; Li, Jiao; Chudhary, Maryam; Ren, Xiang; Kong, Li

doi:10.1007/s00441-020-03267-w

Cited by 35 publications

(25 citation statements)

References 21 publications

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“…Proteomic analysis identified GLO1 as a protein differentially expressed in cells treated with sulforaphane [209]. Sulforaphane inhibited AGEs-derived pericyte damage [210] and delayed diabetes-induced retinal photoreceptor cell degeneration in streptozotocin-injected mice [211]. In addition, pyridoxamine, an MG scavenger that inhibits AGEs formation but also increases GLO1 activity [212], prevented the development of retinopathy in streptozotocin-induced diabetic rats [213].…”

Section: Glyoxalase 1 Activity In Ocular Tissuesmentioning

confidence: 99%

Glyoxalase System as a Therapeutic Target against Diabetic Retinopathy

et al. 2020

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Hyperglycemia, a defining characteristic of diabetes, combined with oxidative stress, results in the formation of advanced glycation end products (AGEs). AGEs are toxic compounds that have adverse effects on many tissues including the retina and lens. AGEs promote the formation of reactive oxygen species (ROS), which, in turn, boost the production of AGEs, resulting in positive feedback loops, a vicious cycle that compromises tissue fitness. Oxidative stress and the accumulation of AGEs are etiologically associated with the pathogenesis of multiple diseases including diabetic retinopathy (DR). DR is a devastating microvascular complication of diabetes mellitus and the leading cause of blindness in working-age adults. The onset and development of DR is multifactorial. Lowering AGEs accumulation may represent a potential therapeutic approach to slow this sight-threatening diabetic complication. To set DR in a physiological context, in this review we first describe relations between oxidative stress, formation of AGEs, and aging in several tissues of the eye, each of which is associated with a major age-related eye pathology. We summarize mechanisms of AGEs generation and anti-AGEs detoxifying systems. We specifically feature the potential of the glyoxalase system in the retina in the prevention of AGEs-associated damage linked to DR. We provide a comparative analysis of glyoxalase activity in different tissues from wild-type mice, supporting a major role for the glyoxalase system in the detoxification of AGEs in the retina, and present the manipulation of this system as a therapeutic strategy to prevent the onset of DR.

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Section: Glyoxalase 1 Activity In Ocular Tissuesmentioning

confidence: 99%

Glyoxalase System as a Therapeutic Target against Diabetic Retinopathy

et al. 2020

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“…Rescue assays indicated that TXNIP overexpression offset the effects of circFTO silencing on the viability, angiogenesis, and BRB of HG-treated RVECs. Previous studies have also reported that TXNIP was highly expressed in diabetic complications (Xu et al, 2013;Lv et al, 2020). For example, the inhibition of the p38/TXNIP/NF-κB pathway by melatonin is suggested to maintain the inner blood-retinal barrier in DR (Tang et al, 2021).…”

Section: Discussionmentioning

confidence: 94%

Circular Ribonucleic Acid circFTO Promotes Angiogenesis and Impairs Blood–Retinal Barrier Via Targeting the miR-128-3p/Thioredoxin Interacting Protein Axis in Diabetic Retinopathy

Guo

Xiao

Ren

et al. 2021

Front. Mol. Biosci.

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Background: Increasing attention has been attracted by the role of circular RNAs (circRNAs) in ocular diseases. Previous study has revealed that circ_0005941 (also known as circFTO, an alpha-ketoglutarate–dependent dioxygenase) was upregulated in the vitreous humor of diabetic retinopathy (DR), while its underlying mechanism in DR remains unknown.Methods: Retinal vascular endothelial cells (RVECs) treated with high glucose (HG) were used to establish the DR cell model. The in vivo assays were conducted using streptozotocin-induced diabetic mice. The circular structure and stability of circFTO were identified by Sanger sequencing and RNase R treatment. RT-qPCR analysis was used to detect the RNA expression. The levels of the mRNA-encoded protein thioredoxin-interacting protein (TXNIP) or angiogenesis-associated proteins (VEGFA, PDGF, and ANG2) and blood–retinal barrier (BRB)-related proteins (ZO-1, Occludin, and Claudin-5) were measured by Western blot. The viability of RVECs was measured using CCK-8 assays. The angiogenesis of RVECs was assessed using tube formation assays in vitro. Endothelial permeability assays were conducted to examine the function of the BRB. The binding between genes was explored using RNA pulldown and luciferase reporter assays.Results: CircFTO was upregulated in HG-treated RVECs. CircFTO deficiency reversed the HG-induced increase in the viability and angiogenesis of RVECs and alleviated HG-mediated impairment of the BRB. MiR-128-3p bound with circFTO and was downregulated in HG-treated RVECs. TXNIP was a downstream target gene of miR-128-3p. TXNIP was highly expressed in the DR cell model. Rescue assays revealed that circFTO promoted angiogenesis and impaired the blood–retinal barrier by upregulating TXNIP. In the DR mouse model, circFTO silencing inhibited angiogenesis and promoted BRB recovery in vivo.Conclusion: CircFTO promotes angiogenesis and impairs the blood–retinal barrier in vitro and in vivo by binding with miR-128-3p to upregulate TXNIP in DR.

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“…With respect to the oral administration of Trx‐1, it had been demonstrated that indomethacin‐induced gastric injury was reduced by daily food intake of sake yeast‐derived Trx‐1 molecule for 3 days (Nakajima et al., 2012 ). In addition, it was demonstrated that sulforaphane, which induces Trx protein, has protective effects on diet‐induced metabolic syndrome and diabetes (Lv et al., 2020 ; Tanito et al., 2005 ; Tian et al., 2021 ), whereas the effects of exogenous hTrx‐1 on genetically severe diabetes are unknown. In the present study, we administered exogenous hTrx‐1 to Akita mice and evaluated changes in the diet behavior, body weight, and blood glucose control.…”

Section: Discussionmentioning

confidence: 99%

“…The inhibition of TXNIP expression, inflammation, and ER stress through the activation of the adenosine monophosphate‐activated protein kinase (AMPK) pathway establishes a protective effect against retinal neurodegeneration in diabetes. This may occur through sulforaphane treatment, which is abundant in broccoli and cabbage and induces the production of Trx protein (Lv et al., 2020 ; Tanito et al., 2005 ). Another natural compound, bakuchiol, exhibits multiorgan protective properties owing to its antioxidative and anti‐inflammatory activities.…”

Section: Introductionmentioning

confidence: 99%