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Zhenya Gao, Yanming Huang, Yuan Kang, Yiwen Li, Rong Wen; Mesencephalic astrocyte-derived neurotrophic factor (MANF) up-regulates CHOP and ATF6 in the rat retina. Invest. Ophthalmol. Vis. Sci. 2016;57(12):4391.
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© ARVO (1962-2015); The Authors (2016-present)
We have shown previously that recombinant human MANF protects photoreceptors in a retinal degeneration rat model carrying the S334ter rhodopsin mutation. In the present work, we examined the effects of MANF on the expression of 5 ER-stress markers, including BiP, IRE1α, PERK, ATF6, and CHOP, in rat retina.
Recombinant human MANF was expressed in E. coli and purified. MANF (10 µg in 3 µl) was intravitreally injected to the left eyes, and the right eyes were injected with 3 µl PBS (phosphate buffered saline) as controls. The levels of ER stress markers BiP, IRE1α, PERK, ATF6, and CHOP, were assessed by Western blot analysis.
We first examined the expression levels of BiP, IRE1α, PERK, ATF6, and CHOP in the retinas of the S334ter (line 3) rats during rapid photoreceptor degeneration from postnatal day (PD) 6 to PD 20. Among the 6 markers, only the level of PERK showed a decrease from PD 6 to PD12. Surprisingly, MANF treatment induced a dramatic increase in ATF6 by 6 hr post injection (injected at PD9). The increase in ATF6 then rapidly declined to control level by 12 hr post injection. In addition, a significant increase in CHOP was detected at 6 hr, peaked at 12 hr, and lasted to 48 hr post injection. No significant changes were seen in the other 4 proteins. Similar increases in ATF6 and CHOP were observed in wild-type Sprague Dawley rats after MANF injection.
No significant changes in ER stress marker were found during the rapid photoreceptor degeneration in the S334ter-3 rats, suggesting that ER stress does not play a major role in photoreceptor degenerations in this model. Intravitreal injection of MANF significantly induces the levels of ATF6 and CHOP.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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