Ginkgo Biloba Standardized Extract EGb 761 Reduces Light and Toxin-Induced Photoreceptor Cell Damage via Regulating Oxidative Stress and Autophagy.
TL;DR
EGb 761 exerts a protective effect on photoreceptor cell damage in retinal degeneration and is associated with a modification of the AMPK/ERK signaling pathway that regulates oxidative stress and autophagy.
Abstract
Purpose
Retinal degeneration (RD) is the common ocular pathogenesis characterized by photoreceptor cell dysfunction. Increasing evidence has shown that the accumulation of 4-hydroxynonenal (4-HNE) is closely associated with RD. Ginkgo biloba special extract EGb 761 has been widely used to prevent and treat certain diseases. In this study, we investigated the effect of EGb 761 on photoreceptor cell damage in retinal degeneration and related mechanism.
Methods
Balb/c mice and 661w cells were used in vivo and in vitro. CCK8 was used to measure the cell viability after 4-HNE or EGb 761 treatment. Apoptosis was evaluated by TUNEL staining. Related gene expression was measured by qRT-PCR and Western blot. Autophagy was observed by TEM and autophagy flux. ROS production was measured using the DCFH-DA probe.
Results
Electroretinography and H&E staining showed that retinal function and morphology were impaired and the expression of LC3 and p62 was decreased or increased and the expressions of anti-oxidative stress-related genes Trx1, Sod2 and Glrx1 were reduced after light damage, EGb 761 treatment ameliorated these processes. After 4-HNE treatment in vitro, the fraction of apoptotic cells was increased and the expression of Bax was increased and Bcl2 was decreased. ROS generation was increased and the expression of Sod2 and Glrx1 was reduced. Furthermore, autophagy was dysregulated, the expression of p62 was increased, and the LC3II/LC3I level was decreased. TEM and autophagic flux showed that autophagosomes accumulated. EGb 761 treatment alleviated these impairments. However, apoptotic cells increased significantly, ROS generation increased and the expression of p-AMPK, p-ERK and Nrf2 was decreased after AMPK inhibitor Compound C treatment, compared with 4-HNE and EGb 761 alone treatment groups.
Conclusion
EGb 761 exerts a protective effect on photoreceptor cell damage in retinal degeneration. This process was associated with a modification of the AMPK/ERK signaling pathway that regulates oxidative stress and autophagy.