Neuroprotective effect of overexpression of thioredoxin on photoreceptor degeneration in Tubby mice

• Main Authors: Li Kong, Xiaohong Zhou, Feng Li, Juni Yodoi, James McGinnis, Wei Cao
• Format: Article
• Language: English
• Published: Elsevier 2010-06-01
• Series: Neurobiology of Disease
• Subjects: Trx; Tubby; Retina; Degeneration; Oxidative stress; Neurotrophins
• Online Access: http://www.sciencedirect.com/science/article/pii/S0969996110000665

The Tubby mouse is a phenotypic model for sensorineural deafness and retinal dystrophy including Usher syndrome type 1. Thioredoxin is a small 13 kDa protein which, when ubiquitously expressed as a transgene in the mouse, provides protection against multiple disease states including light-induced and oxidative stress-induced neurodegeneration and is down-regulated in the Tubby retina. We tested if overexpression of human thioredoxin in the Tubby mouse inhibits retinal degeneration and loss of visual function. Electroretinography, immunocytochemistry, quantitative histology, RT-PCR and Western blots were used to obtain data which showed that thioredoxin overexpression prevented loss of photoreceptors and retinal function. Analysis of signal pathways showed that thioredoxin up-regulated neurotrophic factors BDNF and GDNF and activated survival signaling pathways Akt, Ras/Raf1/ and the ERKs while inhibiting the ASK1/JNK apoptosis pathway. Relationships between the Tubby gene, its pathological phenotype and regulation of the thioredoxin system remain to be established.