Kaempferol is a flavonoid with anticancer and anti-metastasis activity in different cancer-cell lines. However, the underlying mechanisms by which kaempferol acts on human retinal pigment epithelial (ARPE-19) cells remain unclear. In this study, we demonstrated that kaempferol inhibited migration and invasion in ARPE-19 cells at non-toxic dosages. We discovered that kaempferol obviously reduced the enzyme activity and protein expression of matrix metalloproteinase-2 by increasing the phosphorylated levels of extracellular signal-regulated kinases 1/2 (ERK1/2) signaling pathways. Additionally, ERK1/2-specific inhibitor PD98059 significantly reversed kaempferol's inhibitory effects on migration and expression of MMP-2 in ARPE-19 cells. Overall, our results are the first to demonstrate that kaempferol is capable of inhibiting cell migration by targeting ERK1/2 signaling in human retinal pigment epithelial cells. K E Y W O R D S ERK1/2 signaling, kaempferol, migration, MMP-2

Fisetin, a diatery flavonoid, been reported that possess anticancer effects in various cancers. The purpose of the study was to investigate the antitumor effects of fisetin in cultured uveal melanoma cell lines and compared with normal retinal pigment epithelial (RPE) cells. MTT assay was used for evaluating cytotoxic effects of fisetin. Flow cytometry study was used for the determination of apoptosis. JC-1 fluorescent reader was used to determine mitochondrial transmembrane potential changes. The results shown that fisetin dose-dependently decreased the cell viability of uveal melanoma cells but not influenced the cell viability of RPE cells. Apoptosis of uveal melanoma cells was induced by fisetin efficiently. Fisetin inhibited antiapoptotic Bcl-2 family proteins and damaged the mitochondrial transmembrane potential. The levels of proapoptotic Bcl-2 proteins, cytochrome c, and various caspase activities were increased by fisetin. In conclusion, fisetin induces apoptosis of uveal melanoma cells selectively and may be a promising agent to be explored for the treatment of uveal melanoma.

The purpose of the current study was to evaluate the incidence of glaucoma in patients diagnosed with sensorineural hearing loss (SNHL) via the application of the National Health Insurance Research Database in Taiwan. A retrospective cohort study was conducted. Patients with a diagnosis of SNHL were enrolled in the study group after an exclusion procedure and a propensity score matched group without SNHL was served as the control group with a 1:2 ratio. The main outcome was regarded as the emergence of glaucoma diagnostic codes. Cox proportional hazard regression was applied to analyze the incidence and adjusted hazard ratio (aHR) of glaucoma in the multivariate model. A total of 15,686 patients diagnosed with SNHL were enrolled in the study group while another 31,372 non-SNHL individuals served as the control group. There were 444 glaucoma events in the study group and 647 glaucoma events in those non-SNHL individuals after the follow-up interval of 16 years. The study group demonstrated a significantly higher aHR compared to the control group after adjusting for multiple possible risk factors. In the subgroup analysis, both the normal tension glaucoma and angle closure glaucoma subgroups revealed a higher aHR in the study group. In conclusion, the patients with SNHL demonstrated a higher incidence of developing glaucoma. Moreover, the incidence was more prominent for patients diagnosed with normal tension glaucoma and angle closure glaucoma.