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Lalit Singh, Takhellambam Devi, Diabetic Retinopathy; TXNIP regulates neurotrophic factor expression and neuronal injury in early diabetic retinopathy. Invest. Ophthalmol. Vis. Sci. 2013;54(15):270. doi: https://doi.org/.
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We have recently published that the pro-oxidant thioredoxin interacting protein (TXNIP) is significantly up-regulated in the diabetic retina in vivo and mediates cellular oxidative stress and retinal inflammation. The purpose of this study is to investigate the role TXNIP plays in neurotrophic factor expression and neuronal injury in early diabetic retinopathy (DR).
Streptozotocin (STZ)-induced diabetic and age-matched normal rats were maintained for 8 weeks. Subsequently, retinas were harvested and analyzed for gene expression by real time quantitative PCR and immunohistochemistry. To knock down TXNIP, scrambled RNA and siTXNIP were injected intravitreally in diabetic rat retinas.
We observe that TXNIP, iNOS, radial GFAP (Muller cell (MC) activation) and protein s-nitrosylation (SNO) are increased in diabetic rat retinas when compared with normal rats. These results suggest that TXNIP up-regulation correlates with retinal oxidative/nitrosative (ROS/RNS) stress and MC activation. In addition, we found that the mRNA level of brain-derived neurotrophic factor (BDNF) is not altered; however, the expression of its high affinity receptor TrkB and that of glia derived neurotrophic factor (GDNF) are significantly increased. Conversely, the mRNA levels of dendritic spine protein synaptopodin and tyrosine hydroxylase (TH), a marker for dopaminergic inter-neurons, are down-regulated in DR indicating neuronal injury. Finally, knock down of TXNIP by siRNA reduces several molecular abnormalities of early DR.
We propose that TXNIP expression is critical in the initiation and development of early DR. Therefore, TXNIP represents a novel therapeutic target to ameliorate blinding ocular complications of diabetes.
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