Systemic alterations in leukocyte subsets and the protective role of NKT cells in the mouse model of diabetic retinopathy

Suvas, Pratima Krishna; Liu, Li; Rao, Pushpa; Steinle, Jena J.; Suvas, Susmit

doi:10.1016/j.exer.2020.108203

Cited by 6 publications

(2 citation statements)

References 55 publications

(54 reference statements)

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“…The mice were randomly divided into the NC group (the control group ate a normal diet without any treatment; n = 10), DM group (diabetic group, intraperitoneal injection of STZ into mice induced diabetes; n = 15), DM + oe-Sestrin2 group (2 µg oe-Sestrin2 was injected into diabetic mice intravitreally; n = 15), DM + oe-Sestrin2 + erastin group (DM + oe-Sestrin2-treated mice were intraperitoneally injected with 20 mg/kg of the ferroptosis activator erastin three times a week for 4 weeks (Menon et al 2022 ); n = 15) and DM + oe-Sestrin2 + 3-MA group (DM + oe-Sestrin2-treated mice were intraperitoneally injected with 15 mg/kg of the autophagy inhibitor 3-methyladenine (3-MA) three times a week for 4 weeks (Bo et al 2020 ); n = 15). Diabetes was induced by intraperitoneal injection of 60 mg/kg streptozotocin (STZ) for 5 consecutive days (Suvas et al 2020 ; Zhang et al 2009 ). Blood glucose was monitored on the 7th day, and the model was established when blood glucose was ≥ 16.7 mmol/L, and used for treatment experiments in the STZ-treated groups.…”

Section: Methodsmentioning

confidence: 99%

Sestrin2 ameliorates diabetic retinopathy by regulating autophagy and ferroptosis

Xi,

Chen,

et al. 2024

J Mol Histol

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Diabetic retinopathy (DR) is a serious microvascular complication of diabetes. The aim of this study was to explore the effect of Sestrin2 on DR through the regulation of autophagy and ferroptosis levels and its mechanism. In vitro and in vivo DR models were established by high glucose (HG) and streptozotocin (STZ) induction of ARPE-19 human retinal pigment epithelial cells and C57BL/6 mice, respectively. In this study, we demonstrated that after HG treatment, the activity of ARPE-19 cells was decreased, the apoptosis rate was increased, endoplasmic reticulum (ER) stress was activated, autophagy levels were decreased, and ferroptosis levels were increased. Overexpression of Sestrin2 enhanced cell viability, reduced apoptosis and ferroptosis, and enhanced autophagy. However, the effect of overexpression of Sestrin2 was attenuated after the addition of the STAT3 phosphorylation activator Colivelin TFA (C-TFA), the mTOR pathway activator MHY1485 or the autophagy inhibitor 3-methyladenine (3-MA). In addition, the effect of Sestrin2 knockdown on cells was opposite to the effect of overexpression of Sestrin2, while the effect of Sestrin2 knockdown was attenuated after treatment with the ER stress inhibitor 4-phenylbutyric acid (4-PBA). Animal experiments also confirmed the results of cell experiments and attenuated the effects of overexpression of Sestrin2 after injection of the ferroptosis activators erastin or 3-MA. Our study revealed that Sestrin2 inhibits ferroptosis by inhibiting STAT3 phosphorylation and ER stress and promoting autophagy levels, thereby alleviating DR.

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Section: Methodsmentioning

confidence: 99%

Sestrin2 ameliorates diabetic retinopathy by regulating autophagy and ferroptosis

Xi,

Chen,

et al. 2024

J Mol Histol

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“…Recruitment of numerous leukocytes to the DR-related vasculature causes endothelial cell impairment or death and subsequent BRB breakdown [24]. An in vivo study found that leukocyte subsets induce retinal endothelial cell death as a leading cause of BRB damage in early DR, suggesting the role of natural killer T cells in modulating the pathophysiology of DR [25]. When leukostasis occurs, vasodilatation and inflammation can induce early BRB breakdown, eventually leading to retinal endothelial cell damage and death [26].…”

Section: Retinal Endothelial Cell Deathmentioning

confidence: 99%

Frontiers in Understanding the Pathological Mechanism of Diabetic Retinopathy

Zhan

2023

Med Sci Monit

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The retina is a light-sensitive membrane responsible for optical signal reception and concatenation with the optic nerve. Retinal damage causes blurred vision or visual dysfunction. Diabetic retinopathy (DR) is a common microvascular complication of diabetes mellitus (DM) that is induced by the interaction of multiple factors and mechanisms. Hyperglycemia and hypertension are potential risk factors for DR. With the growing number of DM patients, the incidence of DR increases if DM is untreated. Epidemiological data show that DR is a leading cause of blindness in working-aged adults. Regular ophthalmological check-ups, laser treatment, and interdisciplinary consultation for reducing visual atrophy can help prevent and treat DR. Although the pathogenesis of DR is complex, and the exact pathological mechanism of DR needs to be further elucidated to promote new drug research and development against DR. The entire pathological process of DR involves increased oxidative stress (microvascular dysfunction, mitochondrial dysfunction) and chronic inflammation (inflammatory infiltration, cell necrosis) and impairment of the renin-angiotensin system (microcirculation dysregulation). This review aims to summarize the pathological mechanisms underlying the development of DR to improve clinical diagnosis and effective treatment of DR.

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