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.

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

Abnormal proliferation and motility of retinal pigment epithelial cells leads to proliferative vitreoretinopathy (PVR). Melatonin is a known effective antitumour and anti‐invasive agent, but whether it affects the formation and underlying mechanisms of PVR remains unclear. In this study, the results of the MTT assay, colony formation and propidium iodide (PI) staining with flow cytometry revealed that melatonin dose dependently inhibited epidermal growth factor (EGF)‐induced proliferation of human ARPE‐19 cells. Furthermore, melatonin reduced EGF‐induced motility by suppressing cathepsin S (CTSS) expression. Pretreatment with ZFL (a CTSS inhibitor) or overexpression of CTSS (pCMV‐CTSS) significantly inhibited EGF‐induced cell motility when combined with melatonin. Epidermal growth factor induced the phosphorylation of AKT(S473)/mTOR (S2448) and transcription factor (c‐Jun/Sp1) signaling pathways. Pretreatment of LY294002 (a PI3K inhibitor) or rapamycin (an mTOR inhibitor) markedly reduced EGF‐induced motility and p‐AKT/p‐mTOR/c‐Jun/Sp1 expression when combined with melatonin. Taken together, these data indicate that melatonin inhibited EGF‐induced proliferation and motility of human ARPE‐19 cells by activating the AKT/mTOR pathway, which is dependent on CTSS modulation of c‐Jun/Sp1 signalling. Melatonin may be a promising therapeutic drug against PVR.

Background Age-related macular degeneration (AMD) leads to gradual central vision loss and eventual irreversible blindness. Melatonin, an endogenous hormone, exhibits anti-inflammatory and antitumor effects; however, the role it plays in AMD remains unclear. Herein, we investigated the anti-AMD molecular mechanism of melatonin after sodium iodate (NaIO3) treatment of ARPE-19 cells in vitro and in animal models with the goal of improving the therapeutic effect. Results The in vitro results showed that melatonin protected against NaIO3-induced cell viability decline, mitochondrial dysfunction and apoptosis in ARPE-19 cells, and melatonin also alleviated NaIO3-induced reactive oxygen species (ROS) production, mitochondrial dysfunction and mitophagy activation. Melatonin reduced NaIO3-induced mitophagy activation through HIF-1α-targeted BNIP3/LC3B transcription, whereas ROS inhibition realized with N-acetylcysteine (NAC, a ROS inhibitor) combined with melatonin reduced the effect of NaIO3 on mitophagy. An animal model of AMD was established to confirm the in vitro data. Mouse tail vein injection of NaIO3 and melatonin was associated with enhanced repair of retinal layers within 7 days, as observed by optical coherence tomography (OCT) and hematoxylin and eosin (H&E) staining. A reduction in BNIP3 and HIF-1α levels, as determined by immunohistochemistry (IHC) assay, was also observed. Conclusions These results indicate that melatonin attenuated NaIO3-induced mitophagy of ARPE-19 cells via reduction in ROS-mediated HIF-1α targeted BNIP3/LC3B signaling in vitro and in vivo. Melatonin may be a potential therapeutic drug in the treatment of AMD.

This patient presented with excessive pain, lid swelling, erythema, heat and limitations of extraocular movement (OD) nine days after a scleral buckle (SB) and pneumopexy surgery. Complicated buckle infection with endophthalmitis was impressed. Bacterial culture yielded methicillin-resistant Staphylococcus aureus. A choroidal abscess was identified 1 week after the episode. Complete visual recovery from hand motion to 20/30 (OD) was achieved with buckle removal, subconjunctival and intravitreal antibiotics. Endophthalmitis and choroidal abscess formation after SB surgery is extremely rare. Host factors including ulcerative colitis may play a role in causing the severe buckle infection of this patient.

The aim of the current study is to evaluate the possible correlation between the single-nucleotide polymorphisms (SNP) of HOX transcript antisense intergenic RNA (HOTAIR) and the clinical characteristics of diabetic retinopathy (DR). Four loci of HOTAIR SNPs, including rs920778 (T/C), rs12427129 (C/T), rs4759314 (A/G), and rs1899663 (G/T), were genotyped via the TaqMan allelic discrimination for 276 DR individuals and 452 non-DR patients. The distribution frequency of HOTAIR SNP rs12427129 CT [adjusted odds ratio (AOR): 1.571, 95% CI: 1.025–2.408, p = 0.038], HOTAIR SNP rs12427129 CT+TT (AOR: 1.611, 95% CI: 1.061–2.446, p = 0.025), and HOTAIR SNP rs1899663 TT (AOR: 2.443, 95% CI: 1.066–5.595, p = 0.035) were significantly higher in the DR group. Moreover, the proliferative diabetic retinopathy (PDR) subgroup revealed a significantly higher distribution of HOTAIR SNP rs12427129 CT+TT (AOR: 2.016, 95% CI: 1.096–3.710, p = 0.024) and HOTAIR SNP rs1899663 TT (AOR: 4.693, 95% CI: 1.765–12.479, p = 0.002), and the distribution frequencies of HOTAIR SNP rs12427129 CT (AOR: 3.722, 95% CI: 1.555–8.909, p = 0.003), HOTAIR SNP rs12427129 CT+TT (AOR: 4.070, 95% CI: 1.725–9.600, p = 0.001), and HOTAIR SNP rs1899663 TT (AOR: 11.131, 95% CI: 1.521–81.490, p = 0.018) were significantly higher in the female PDR subgroup. Regarding the clinical characters, the DR patients with HOTAIR SNP rs1899663 GT+TT revealed a significantly shorter duration of diabetes compared to the DR patients with HOTAIR SNP rs1899663 GG (10.54 ± 8.19 versus 12.79 ± 7.73, p = 0.024). In conclusion, HOTAIR SNP rs12427129 and rs1899663 are strongly correlated to the presence of DR, especially for a female with PDR.

Low-dose IVTA therapy may be valuable for preserving the vision of PCV patients, while vPDT or anti-VEGF is not affordable/available or of those with underlying diseases for whom anti-VEGF therapy is with intolerable risk.