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J. F. McGinnis, X. Zhou, L. Kong, F. Li, J. Yodoi, W. Cao; Inherited Photoreceptor Degeneration Is Delayed and Vision Preserved by Over Expression of Thioredoxin in the Tubby Mouse. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4930. doi: https://doi.org/.
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Thioredoxin (Trx) has neurotrophic factor-like activity and may play a crucial role in maintaining neuronal cell integrity. In this study, the neuroprotective effect of Trx on photoreceptor degeneration in tubby (tub) mouse, a phenotypical model of sensorineural deafness/retinal dystrophic syndromes, was examined.
Human-Trx transgenic (Tg-Trx) mice were crossed with homozygous tubby mice. Protective effects of the over expression of Trx were evaluated morphologically by quantitative histology and functionally by electroretinography (ERG). Immunohistochemistry was performed to localize the expression of Trx in the retina. Real-Time qPCR, RT-PCR and Western blot analysis were used to examine the expression of the Trx mRNA and its protein. In addition, the levels of selected neuroprotective proteins and their mRNAs were evaluated in the retinas of control and experimental mice.
Our data clearly demonstrate a significant overexpression of the mRNA for Trx and its protein in the retinas of Tg-Trx/tub mice compared to that of tubby mice. At P34, the amplitude of the ERG b-wave and the outer nuclear layer thickness were significantly increased in Tg-Trx/tub mice (p<0.01). Overexpression of Trx extensively up-regulated retinal levels of brain-derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF) and fibroblast growth factor-basic (FGF-b) in Tg-Trx/tub mice, reaching levels observed in wild type mice.
Trx strongly delays photoreceptor degeneration and preserves visual function in tubby mice. BDNF, GDNF and FGF-b may be involved in the mechanism of Trx-mediated photoreceptor protection in this model.
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