Mesencephalic astrocyte-derived neurotrophic factor upregulates CHOP and ATF6 in the rat retina with retinitis pigmentosa.

Abstract

Purpose: In the current work, we investigated the potential protective function of MANF against the degeneration of RP in S334ter-3 rats and the mechanism underlying these effects.

Methods: The left eye of rat was injected with MANF, and the right eye injected PBS as a control. The levels of those ER stress associated proteins were determined by western blot analysis.

Results: First, those ER stress associated proteins were detected in S334ter-3 rats. Among these proteins, a decrease in the expression of PERK was only showed from PD 6 to PD 12. Surprisingly, a dramatic increase of ATF6 was induced by injection MANF. Then, the expression of ATF6 protein declined rapidly to the control eye. Furthermore, a remarkable increase in the expression of CHOP was examined at 6 h, which peaked at 12 h and maintained the level until 48 h. At the same time, CHOP was detected in Müller cells but not in photoreceptor; nevertheless, photoreceptor survival clearly improved. The increasing expressions of CHOP and ATF6 in SD rats were similar to the changes in S33ter-3 rats after injection MANF.

Conclusions: These results indicate that MANF may play an important role in protecting photoreceptor degeneration in RP.