Genetic association of diabetic retinopathy with long noncoding RNA CDKN2B-AS1 gene polymorphism.

AIM: We attempted to test the influences of cyclin dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1) gene polymorphisms on the susceptibility to Diabetic retinopathy (DR). METHODS: Five single-nucleotide polymorphisms (SNPs) of the CDKN2B-AS1 gene, rs564398, rs1333048, rs1537373, rs2151280, and rs8181047 were examined in 280 DR cases and 455 DR-free diabetic controls. RESULTS: Among these loci tested, we demonstrated that diabetic carriers of at least one polymorphic allele (G) of rs2151280 (AG and GG; AOR, 1.613; 95% CI, 1.040-2.501; p = 0.033) are more susceptible to proliferative DR but not non-proliferative DR. This genetic association with the risk of developing proliferative DR was further strengthened in homozygotes for the polymorphic allele (G) of rs2151280 (GG; AOR, 2.194; 95% CI, 1.117-4.308; p = 0.023). We detected a significant association of the polymorphic allele (G) of rs2151280 with proliferative DR patients (OR, 1.503; 95% CI, 1.112-2.033; p = 0.008) but not with the entire DR or non-proliferative DR group. Moreover, as compared to those who do not possess the polymorphic allele of rs2151280 (AA), DR patients carrying at least one polymorphic allele of rs2151280 (AG + GG) exhibited a lower glomerular filtration rate and HDL cholesterol level, revealing a promotive role of rs2151280 in renal and cardiovascular complications of diabetes. CONCLUSION: Taken together, our findings implicate an impact of CDKN2B-AS1 gene polymorphisms on the progression of DR.

The Genetic Variants of Long Noncoding RNA MEG3 and Its Association to the Clinical Features of Diabetic Retinopathy.

PURPOSE: This study aimed to investigate the potential correlation between the single-nucleotide polymorphism (SNP) of maternally expressed gene 3 (MEG3) and the clinical manifestations of diabetic retinopathy (DR). METHODS: Five loci of MEG3 SNPs including rs4081134 (G/A), rs10144253 (T/C), rs7158663 (G/A), rs3087918 (T/G) and rs11160608 (A/C) were genotyped by TaqMan allelic discrimination in 457 non-DR patients and 280 DR individuals. RESULTS: The distribution frequency of MEG3 SNP rs7158663 GA (AOR: 0.683, 95% CI: 0.478-0.975, p = 0.036) and MEG3 SNP rs7158663 GA + AA (AOR: 0.686, 95% CI: 0.487-0.968, p = 0.032) were significantly lower in the DR group. And the MEG3 SNP rs7158663 GA + AA (AOR: 0.610, 95% CI: 0.377-0.985, p = 0.043) demonstrated a significantly lower distribution frequency in the male DR group. Besides, the DR patients with MEG3 SNP rs7158663 GA + AA genotype showed a significantly lower HbA1c level than the DR patients with MEG3 SNP rs7158663 GG genotype (7.29 ± 1.23 versus 7.74 ± 1.49, p = 0.013). Moreover, in the analysis using data from gene expression data series database, a higher MEG3 level was significantly correlated to a lower miR-182 level in the database (p = 0.0114). CONCLUSIONS: In this study, the distribution frequency of MEG3 SNP rs7158663 GA + AA genotype was lower in DR, while the DR would develop under lower HbA1c level in DM patients with this MEG3 SNP variant.

Tricetin suppresses the cell migration and BMP-6 expression through p38 signaling pathways in human retinal pigment epithelium cells.

Proliferative vitreoretinopathy (PVR) is a visual-threatening disease, which cause from the migration of retinal pigment epithelium (RPE). Tricetin, a family of flavonoids, can inhibit the metastasis of several cancers. Herein, we aim to evaluate the possible effect of tricetin on inhibiting ARPE-19 cells migration. The Boyden chamber assay, wound healing assay, RNA sequencing, and Western blot analysis were applied in our experiment. The results revealed that tricetin inhibited the cell migration abilities of ARPE-19 cells. Moreover, using RNA sequencing technology, we revealed that tricetin repressed bone morphogenetic protein-6 (BMP-6) gene expressions in ARPE-19 cells. Overexpression of BMP-6 resulted in significant restoration of cell migration capabilities of tricetin-treated ARPE-19 cells. Furthermore, tricetin suppressed the phosphorylation of the p38 signaling pathway. Moreover, blocking the p38 pathway also inhibits BMP-6 expression and migration in the ARPE-19 cells. In conclusion, this study revealed that tricetin inhibits the ARPE-19 cell migration mainly via the suppression of BMP-6 expression and p38 signaling pathway.

The Need for Glaucoma Management in Glaucoma Patients with Concurrent Obstructive Sleep Apnea: A Population-Based Cohort Study.

We try to evaluate glaucoma management numbers in patients with both glaucoma and obstructive sleep apnea (OSA) using the National Health Insurance Research Database (NHIRD) of Taiwan. A retrospective cohort study was conducted and patients with glaucoma were enrolled and divided into the OSA and non-OSA populations. A total of 11,778 participants were selected in both the OSA and non-OSA groups. The primary outcomes were the number of anti-glaucomatous medications each year and the total number of glaucoma laser and glaucoma surgeries. The Cox proportional hazard regression was utilized to produce the adjusted hazard ratios (AHR) with corresponding 95% confidence intervals (CI) between the two groups. After a study period of 18 years, 286 and 352 events of laser and surgeries for glaucoma were found in the OSA and non-OSA groups, respectively. After considering the effect of potential confounders, no significant difference concerning the numbers of laser trabeculoplasty, trabeculectomy and tube shunt surgery, cyclodestructive procedure and eyeball removal were found between the two groups (all 95% CIs included one). In addition, the multiple anti-glaucomatous medication usages were similar between the two groups (all p > 0.05) In the subgroup analyses, glaucoma patients older than 60 years and with OSA received significantly lesser trabeculectomy and tube shunt surgery compared to glaucoma patients older than 60 years without OSA (AHR: 0.774, 95% CI: 0.611−0.981) while other analyses revealed insignificant results (all 95% CIs included one). In conclusion, the presence of OSA does not increase the need for glaucoma management.

The association between late-onset keratitis in congenital cytomegalovirus infection: A nationwide population-based cohort study.

AIM: To estimate the relationship between congenital cytomegalovirus (CMV) infection and late-onset keratitis via use of the National Health Insurance Research Database (NHIRD) of Taiwan. METHODS: We yielded this retrospective cohort study and subjects with congenital CMV infection, which according to the diagnostic codes and laboratory exam, were selected as our study group that diagnosed with congenital CMV infection. Each participant in the study group was matched to four individuals without the non-congenital CMV infection by propensity-score matching (PSM) process and the latter served as the control group. The main outcome is the late-onset keratitis that occurs one year after the congenital CMV infection diagnosis. We applied Cox proportional hazard regression to produce the adjusted hazard ratio (HR) and corresponding 95% confidence interval (CI) of late-onset keratitis between two groups. RESULTS: There were 426 (7.4%) and 1,516 (6.5%) events of keratitis in the study and control groups. The study group revealed significantly higher ratio of late-onset keratitis than control group after adjusting many confounders (adjusted HR: 1.14, 95% CI: 1.02-1.27), and the cumulative probability of keratitis in the study group was also higher than control group. For the subgroup analysis, the existence of severe congenital CMV infection was significantly correlated to the late-onset keratitis in individuals with congenital CMV infection (adjusted HR: 1.48, 95% CI: 1.01-2.70; P < 0.05). CONCLUSION: The congenital CMV infection is related to higher rate of late-onset keratitis, especially for those with severe form.

Norcantharidin attenuates epidermal growth factor-induced proliferation, EMT and motility in ARPE-19 cells by modulating the AKT/snail/E-cadherin axis.

AIMS: Norcantharidin (NCTD) is a demethylated derivative of cantharidin demonstrated to have anti-proliferative, anti-inflammatory, and anti-fibrosis properties. The purpose of the current study is to investigate the underlying mechanisms and signaling pathways affected by NCTD in human ARPE-19 cells. MAIN METHODS: Cell growth and rate of proliferation were assayed by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay, colony formation assay, and cell cycle distribution/quantification. Cell motility was detected with in vitro migration assay. The level of epithelial-mesenchymal transition (EMT)-related proteins and mRNA (Snail, Slug, E-cadherin) were detected using Western blotting, real-time quantitative polymerase chain reaction, and immunofluorescence assay. Overexpression of Snail plasmid was determined by transfection assay. KEY FINDINGS: We found that NCTD reduced epidermal growth factor (EGF)-induced ARPE-19 cell viability and proliferation through increasing the p21 and p27 expression and decreasing the cyclin D1 expression. NCTD also inhibited EGF-mediated EMT and cell motility through increased protein and mRNA levels of E-cadherin and decreased Snail in EGF-induced ARPE-19 cells. Overexpression of Snail significantly decreased ARPE-19 cell motility and increased E-cadherin expression in NCTD-treated cells. Additionally, when NCTD was combined with a PI3K inhibitor (LY294002) significantly decreased the p-AKT and Snail expression, and increased the E-cadherin expression of EGF treatment in ARPE-19 cells. SIGNIFICANCE: The current findings revealed that NCTD suppresses the EGF-induced proliferation, motility, and EMT of ARPE-19 cells through inactivation of the AKT-mediated Snail/E-cadherin pathway. NCTD may be a potential preventive agent for proliferative vitreoretinopathy.

Association of Long Noncoding RNA HOTAIR Polymorphism and the Clinical Manifestations of Diabetic Retinopathy.

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.

The use of androgen deprivation therapy for prostate cancer and its effect on the subsequent dry eye disease: a population-based cohort study.

This study aimed to investigate the influence of androgen deprivation therapy (ADT) for the development of dry eye disease (DED) in subjects with prostate cancer via the use of national health insurance research database (NHIRD) of Taiwan. A retrospective cohort study was conducted and patients were selected as prostate cancer with ADT according to diagnostic and procedure codes. Each participant in that group was then matched to one patient with prostate cancer but without ADT and two subject s without prostate cancer and ADT. And a total of 1791, 1791 and 3582 participants were enrolled in each group. The primary outcome was set as the DED development according to the diagnostic codes. Cox proportional hazard regression was applied to calculate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) of ADT and other parameters for DED development. There were 228, 126 and 95 new events of DED developed in the control group, the prostate cancer without ADT group and the prostate cancer with ADT group. The rate of DED in the prostate cancer with ADT group (aHR: 0.980, 95% CI: 0.771-1.246, P= 0.8696) and Prostate cancer without ADT group (aHR: 1.064, 95% CI: 0.855-1.325, P= 0.5766) were not significantly different compared to the control group. In addition, the patients aged 70-79 years old demonstrated a significantly higher incidence of developing DED compared to those aged 50-59 years old (aHR: 1.885, 95% CI: 1.188-2.989, P= 0.0071). In conclusion, the use of ADT did not alter the incidence of subsequent DED.

Melatonin inhibits NaIO3-induced ARPE-19 cell apoptosis via suppression of HIF-1α/BNIP3-LC3B/mitophagy signaling.

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.

Demethoxycurcumin inhibits the cell migration and MMP-2 expression in human retinal pigment epithelial cells by targeting the STAT-3 pathway.

Proliferative vitreoretinopathy (PVR) involves retinal pigment epithelium (RPE) cell proliferation and migration and leads to tractional retinal detachment. Demethoxycurcumin (DMC), a curcuminoid, has anti-inflammatory and anti-tumour properties. However, whether DMC affects the migration of RPE cells and the molecular mechanism of human PVR remains unclear. The aim of the current study was to investigate the effects of DMC on the inhibition of migration and proteinase expression of human ARPE-19 cells. Herein, we provided molecular evidence associated with PVR prevention through DMC by inhibiting ARPE-19 cell migration. We performed gelatin zymography, Western blot and RT-PCR and respectively found that DMC is sufficient to reduce matrix metalloproteinase-2 (MMP-2) activity, protein level and mRNA expression. DMC suppressed the nuclear levels of transcriptional factors specificity protein 1 and c-Fos, which are involved in the modulation of the transcriptional activation of the MMP-2 gene. DMC also inhibited STAT-3 phosphorylation in ARPE-19 cells. Selective STAT-3 induction by a STAT-3 activator, colivelin, reverted MMP activity and protein expression and cell migration, which were reduced in response to DMC. The results proved the inhibitory effect of DMC on RPE cell migration and MMP-2 expression by the down-regulation of the STAT-3 signalling pathway.

Medical Compliance of Fibrate and the Decreased Risk of Age-Related Macular Degeneration in Dyslipidemia-Related Diseases: A Population-Based Cohort Study.

The purpose of the current study is to evaluate the incidence of age-related macular degeneration (AMD) in dyslipidemia-related diseases with or without the use of fibrate. Patients were defined as dyslipidemia-related diseases according to the diagnostic code and lab exam arrangement, then the population was divided into those with fibrate application and those without via 1:2 ratios of propensity-score matching. The primary outcome is the development of AMD after dyslipidemia-related diseases by the Cox proportional hazard regression. Besides, the relationship between the medical compliance of fibrate, presented as medical possession ratio (MPR), and the AMD development was also analyzed. A total of 22,917 patients and 45,834 individuals were enrolled in the study and control groups. There were 572 and 1181 events of any AMD development in the study and control groups which showed identical risk of AMD (aHR: 0.94, 95% CI: 0.85-1.04). However, a reduced risk of any AMD was found in those patients reached a baseline MPR more than 20% (aHR: 0.729, 95% CI: 0.599-0.887, p = 0.0016) and overall MPR more than 5% three years after the diagnosis of dyslipidemia-related diseases (aHR: 0.712, 95% CI: 0.557-0.909, p = 0.0065). Besides, a lower risk of dry-AMD was also found in those patients with the above conditions (aHR: 0.736, 95% CI: 0.599-0.906, p = 0.0038 and aHR: 0.721, 95% CI: 0.557-0.934, p = 0.0133, respectively). In conclusion, the use of fibrate with fair initial medical compliance will decrease the incidence of AMD in patients with dyslipidemia-related diseases, especially for the development of dry-AMD.

Melatonin attenuates epidermal growth factor-induced cathepsin S expression in ARPE-19 cells: Implications for proliferative vitreoretinopathy.

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.

Increased Incidence of Glaucoma in Sensorineural Hearing Loss: A Population-Based Cohort Study.

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 suppresses cell migration through the activation of the ERK signaling pathways in ARPE-19 cells.

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.

Fisetin induces apoptosis through mitochondrial apoptosis pathway in human uveal melanoma cells.

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.

Vision Preservation in Eyes of Polypoidal Choroidal Vasculopathy with Low-Dose Intravitreal Triamcinolone Acetonide.

PURPOSE: To evaluate the efficacy and adverse effects of using low-dose intravitreal triamcinolone acetonide (IVTA) to preserve vision in polypoidal choroidal vasculopathy (PCV) eyes. METHODS: This retrospective chart review study examined 8 eyes of 7 PCV patients, for whom verteporfin photodynamic therapy (vPDT) or antivascular endothelial growth factor (VEGF) therapy was not affordable/available and also with intolerable risk because of underlying cardiovascular and/or cerebrovascular ischemia. Low-dose IVTA (1 mg/0.025 mL) monotherapy was administered and repeated every 4 weeks if intraretinal edema or subretinal fluid persisted. RESULTS: The median follow-up time was 26.4 months. Three eyes (3/8) maintained their initial best-corrected visual acuity and 4 eyes (4/8) exhibited improvement, whereas 1 eye (1/8) sustained some loss. The mean injection number per month was 0.7 for the first 6 months, after which it decreased to 0.4. In regard to adverse effects, intraocular pressure (IOP) of more than 21 mmHg was noted as persisting for a few weeks in 4 eyes and that of more than 30 mmHg was noted once in 1 eye. The increased IOP was adequately controlled by using IOP-lowering agents. Two initially phakic eyes each underwent cataract surgery in the 12th and 14th months after treatment. CONCLUSIONS: 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.

Fisetin inhibits epidermal growth factor-induced migration of ARPE-19 cells by suppression of AKT activation and Sp1-dependent MMP-9 expression.

Purpose: Proliferative vitreoretinopathy (PVR) can result in abnormal migration of RPE cells. Fisetin is a naturally occurring compound that has been reported to have antitumor effects, but its effects on epidermal growth factor (EGF)-induced cell migration and the underlying mechanisms remain unclear. Methods: Effects of fisetin on EGF-induced cell viability and migration were examined with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and in vitro migration assays. Reverse transcription-PCR (RT-PCR) and immunoblotting were performed to evaluate matrix metallopeptidase-9 (MMP-9) expression and activation of specificity protein-1 (Sp1) and protein kinase B (AKT) in ARPE-19 cells treated with EGF and with or without fisetin. Luciferase and chromatin immunoprecipitation (ChIP) assays were performed to examine Sp1 transcription activity and MMP-9 binding activity. Results: Fisetin did not affect ARPE-19 cell viability and significantly inhibited the EGF-induced migration capacity of ARPE-19 cells. Furthermore, fisetin exerted an antimigratory effect and suppressed MMP-9 mRNA and protein expression. Treatment with EGF induced phosphorylation of AKT and expression of MMP-9 and Sp1. Fisetin combined with LY294002 (an inhibitor of AKT) prevented the EGF-induced migration involved in downregulation of Sp1 and MMP-9 expression. Luciferase and ChIP assays suggested that fisetin remarkably decreased the EGF-induced transcription activity of MMP-9 and Sp1 and inhibited EGF-mediated Sp1 from directly binding to the MMP-9 promoter in ARPE-19 cells. Conclusions: Fisetin inhibited EGF-induced cell migration via modulation of AKT/Sp1-dependent MMP-9 transcriptional activity. Therefore, fisetin may be a potential agent in the treatment of migratory PVR diseases.

Early vitreomacular separation with delayed macular hole closure after ocriplasmin treatment.

Based on the indications, one-third to one-half of patients can achieve full-thickness macular hole (FTMH) closure with or without the separation of vitreomacular adhesion (VMA) within 28 days of ocriplasmin treatment. The authors report the case of a 63-year-old man with early VMA separation and delayed FTMH closure after ocriplasmin treatment. Four weeks posttreatment, the posterior vitreous detachment occurred at the optic disk, and the macular hole (MH) started decreasing thereafter. MH closure was finally achieved at 10 weeks posttreatment, leaving minimal subretinal fluid. The patient's vision improved from 0.8 LogMAR (pretreatment) to 0.3 LogMAR (12 weeks posttreatment). This case suggests that FTMH closure can be achieved within 28 days of ocriplasmin treatment.

Methicillin-resistant Staphylococcus aureus buckle infection complicated by endophthalmitis and presumed choroidal abscess in a patient with ulcerative colitis.

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.