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.