Overexpression of serine racemase in retina and overproduction of D-serine in eyes of streptozotocin-induced diabetic retinopathy

Jiang, Haiyan; Fang, Junxu; Wu, Bo; Yin, Guibin; Sun, Lin; Qu, Jia; Barger, Steven W.; Wu, Shengzhou

doi:10.1186/1742-2094-8-119

Cited by 30 publications

(27 citation statements)

References 47 publications

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“…In contrast, the physiological and pathological roles of SR/ d ‐serine in the retina are relatively scant, but SR/ d ‐serine has been implicated in diabetic retinopathy (Jiang et al . , , ). SR expression has been reported in retinal ganglion cells and glial cells (Stevens et al .…”

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confidence: 99%

Serine racemase deficiency attenuates choroidal neovascularization and reduces nitric oxide and VEGF levels by retinal pigment epithelial cells

Jiang

Liu

et al. 2017

Journal of Neurochemistry

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Choroidal neovascularization (CNV) is a leading cause of blindness in age-related macular degeneration. Production of vascular endothelial growth factor (VEGF) and macrophage recruitment by retinal pigment epithelial cells (RPE) significantly contributes to the process of CNV in an experimental CNV model. Serine racemase (SR) is expressed in retinal neurons and glial cells, and its product, d-serine, is an endogenous co-agonist of N-methyl-d-aspartate receptor. Activation of the receptor results in production of nitric oxide ( NO), a molecule that promotes retinal and choroidal neovascularization. These observations suggest possible roles of SR in CNV. With laser-injured CNV mice, we found that inactivation of SR-coding gene (Srr ) significantly reduced CNV volume, neovascular density, and invading macrophages. We exploited the underlying mechanism in vivo and ex vivo. RPE from wild-type (WT) mice expressed SR. To explore the possible downstream target of SR inactivation, we showed that choroid/RPE homogenates extracted from laser-injured Srr mice contained less inducible nitric oxide synthase and decreased phospho-VEGFR2 compared to amounts in WT mice. In vitro, inflammation-primed WT RPEs expressed more inducible NOS, produced more NO and VEGF than did inflammation-primed Srr RPEs. When co-cultured with inflammation-primed Srr RPE, significantly fewer RF/6A-a cell line of choroidal endothelial cell, migrated to the opposite side of the insert membrane than did cells co-cultured with pre-treated WT RPE. Altogether, SR deficiency reduces RPE response to laser-induced inflammatory stimuli, resulting in decreased production of a cascade of pro-angiogenic cytokines, including NO and VEGF, and reduced macrophage recruitment, which contribute synergistically to attenuated angiogenesis.

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confidence: 99%

Serine racemase deficiency attenuates choroidal neovascularization and reduces nitric oxide and VEGF levels by retinal pigment epithelial cells

Jiang

Liu

et al. 2017

Journal of Neurochemistry

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“…Evidence indicate that NMDA toxicity towards RGCs is enhanced by intravitreal injection of D‐serine or glycine, whereas blocking glycine transport or blocking the glycine B binding site with 5, 7‐dichlorokynurenic acid (DCKA) reduces toxicity . Our prior results demonstrate that D‐serine and glutamate are increased in the aqueous humour in the STZ‐induced diabetic rats . In this study, the levels of D‐serine and glutamate in the aqueous and/or vitreous humour in patients with PDR were determined to investigate their potential roles in retina neuronal damage.…”

Section: Introductionmentioning

confidence: 94%

“…16 Our prior results demonstrate that D-serine and glutamate are increased in the aqueous humour in the STZ-induced diabetic rats. 17 In this study, the levels of D-serine and glutamate in the aqueous and/or vitreous humour in patients with PDR were determined to investigate their potential roles in retina neuronal damage.…”

Section: Introductionmentioning

confidence: 99%

Increased D‐serine in the aqueous and vitreous humour in patients with proliferative diabetic retinopathy

Jiang

Du²,

et al. 2014

Clinical Exper Ophthalmology

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“…Normal control rats (nZ6) received injections of citric buffer (vehicle). Ten days after vehicle/STZ injection, only diabetic rats with fasting blood glucose (FBG) over 300 mg/dl were included in the experiments (Jiang et al 2011, Zhao et al 2014. Rats were assigned to one of six groups with six rats in each group and were treated as follows: normal rats treated with vehicle (NMV), diabetic rats treated with vehicle (DMV), diabetic rats treated with insulin at a dose of 4 U/kg (DMI), diabetic rats treated with PCA at a dose of 50 mg/kg (DML), diabetic rats treated with PCA at a dose of 100 mg/kg (DMH) (Harini & Pugalendi 2010), and diabetic rats treated with DMH and insulin at a dose of 4 U/kg (DMHI).…”

Section: Animalsmentioning

confidence: 99%

Protocatechuic acid exerts a cardioprotective effect in type 1 diabetic rats

Semaming¹,

Kumfu²,

Pannangpetch³

et al. 2014

Journal of Endocrinology

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Oxidative stress has been shown to play an important role in the pathogenesis of diabetesinduced cardiac dysfunction. Protocatechuic acid (PCA) is a phenolic compound, a main metabolite of anthocyanin, which has been reported to display various pharmacological properties. We proposed the hypothesis that PCA exerts cardioprotection in type 1 diabetic (T1DM) rats. T1DM was induced in male Sprague-Dawley rats by a single i.p. injection of 50 mg/kg streptozotocin (STZ) and groups of these animals received the following treatments for 12 weeks: i) oral administration of vehicle, ii) oral administration of PCA at a dose of 50 mg/kg per day, iii) oral administration of PCA at a dose of 100 mg/kg per day, iv) s.c. injection of insulin at a dose of 4 U/kg per day, and v) a combination of PCA, 100 mg/kg per day and insulin, 4 U/kg per day. Metabolic parameters, results from echocardiography, and heart rate variability were monitored every 4 weeks, and the HbA1c, cardiac malondialdehyde (MDA), cardiac mitochondrial function, and cardiac BAX/BCL2 expression were evaluated at the end of treatment. PCA, insulin, and combined drug treatments significantly improved metabolic parameters and cardiac function as shown by increased percentage fractional shortening and percentage left ventricular ejection fraction and decreased low-frequency:high-frequency ratio in T1DM rats. Moreover, all treatments significantly decreased plasma HbA1c and cardiac MDA levels, improved cardiac mitochondrial function, and increased BCL2 expression. Our results demonstrated for the first time, to our knowledge, the efficacy of PCA in improving cardiac function and cardiac autonomic balance, preventing cardiac mitochondrial dysfunction, and increasing anti-apoptotic protein in STZ-induced T1DM rats. Thus, PCA possesses a potential cardioprotective effect and could restore cardiac function when combined with insulin treatment. These findings indicated that supplementation with PCA might be helpful for the prevention and alleviation of cardiovascular complications in T1DM.

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Overexpression of serine racemase in retina and overproduction of D-serine in eyes of streptozotocin-induced diabetic retinopathy

Cited by 30 publications

References 47 publications

Serine racemase deficiency attenuates choroidal neovascularization and reduces nitric oxide and VEGF levels by retinal pigment epithelial cells

Serine racemase deficiency attenuates choroidal neovascularization and reduces nitric oxide and VEGF levels by retinal pigment epithelial cells

Increased D‐serine in the aqueous and vitreous humour in patients with proliferative diabetic retinopathy

Protocatechuic acid exerts a cardioprotective effect in type 1 diabetic rats

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