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APC can reduce ischemia-induced cytotoxicity both in vitro and in vivo via blocking the activation of caspase-3, -8, and -9. APC may be a promising candidate for protecting the retina from ischemia.

The sympathetic nervous system regulates bone formation and resorption under physiological conditions. However, it is still unclear how the sympathetic nerves affect stem cell migration and differentiation in bone regeneration. Distraction osteogenesis is an ideal model of bone regeneration due to its special nature as a self-engineering tissue. In this study, a rat model of mandibular distraction osteogenesis with transection of cervical sympathetic trunk was used to demonstrate that sympathetic denervation can deplete norepinephrine (NE) in distraction-induced bone callus, down-regulate β3-adrenergic receptor (adrb3) in bone marrow mesenchymal stem cells (MSCs), and promote MSC migration from perivascular regions to bone-forming units. An in vitro Transwell assay was here used to demonstrate that NE can inhibit stroma-derived factor-1 (SDF-1)-induced MSC migration and expression of the migration-related gene matrix metalloproteinase-2 (MMP-2) and downregulate that of the anti-migration gene tissue inhibitor of metalloproteinase-3 (TIMP-3). Knockdown of adrb3 using siRNA abolishes inhibition of MSC migration. An in vitro osteogenic assay was used to show that NE can inhibit the formation of MSC bone nodules and expression of the osteogenic marker genes alkaline phosphatase (ALP), osteocalcin (OCN), and runt-related transcription factor-2 (RUNX2), but knockdown of adrb3 by siRNA can abolish such inhibition of the osteogenic differentiation of MSCs. It is here concluded that sympathetic denervation-induced MSC mobilization in rat mandibular distraction osteogenesis is associated with inhibition of MSC migration and osteogenic differentiation by NE/adrb3 in vitro. These findings may facilitate understanding of the relationship of MSC mobilization and sympathetic nervous system across a wide spectrum of tissue regeneration processes.

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Age-related macular degeneration (AMD), one of the most common causes of visual impairment, often occurrs in the elderly in developed countries. Oxidative stress, autophagy, and apoptosis of retinal pigment epithelial (RPE) cells play roles in the pathogenesis of AMD. In the current study, the protective effect of celastrol against hydrogen peroxide (H 2 O 2 )-induced oxidative stress and apoptosis was investigated using a human RPE cell line . H 2 O 2 inhibited ARPE-19 cells' survival and autophagy and induced their oxidative stress and apoptosis.Compared with the H 2 O 2 group, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay showed that celastrol increased ARPE-19 cells' survival in a dose-and time-dependent manner. Further, studies have suggested that celastrol has antioxidative stress and antiapoptosis effects in H 2 O 2 -treated ARPE-19 cells. Also, cell autophagy is activated by celastrol in H 2 O 2 -treated ARPE-19 cells. Reverse transcription polymerase chain reaction and Western blot showed that celastrol elevated the messenger RNA (mRNA) and protein expression of sirtuin 3 (SIRT3) in H 2 O 2 -induced ARPE-19 cells. Inhibition of the level of SIRT3 by SIRT3 small interfering RNA (siRNA) reversed the effects of celastrol on oxidative stress, autophagy, and apoptosis in H 2 O 2 -induced ARPE-19 cells. In conclusion, these observations suggest that celastrol activates the SIRT3 pathway in RPE cells and protects against H 2 O 2 -induced oxidative stress and apoptosis. K E Y W O R D S autophagy, celastrol, oxidative stress, retinal pigment epithelial cells, sirtuin 3 1 | INTRODUCTION Age-related macular degeneration (AMD) is a common cause of age-related irreversible vision loss among persons older than 50 years of age. It is common in the developed world. 1,2 Ample evidence suggests that retinal pigment epithelial (RPE) cell death and progressive degeneration result in age-related vision loss. 3 There are two stages of AMD progression: early and advanced stages. The primary early target of AMD is RPE cells. The aggregation of extracellular deposits between Bruch's membrane and RPE cells and the change of the pigmentation of the RPE cells are the key clinical features of AMD. 4 Various genetic and environmental risk factors are involved in RPE cell dysfunction in AMD, such as oxidative stress. 5 The elevation of oxidative stress leads to RPE cell apoptosis and hastens AMD onset. 6,7