TRPM4 and TRPV2 are two novel prognostic biomarkers and promising targeted therapy in UVM.

Uveal melanoma (UVM) is the most common primary intraocular malignancy tumor in adults. Almost 50% of UVM patients develop metastatic disease, and is usually fatal within 1 year. However, the mechanism of etiology remains unclear. The lack of prognostic, diagnostic and therapeutic biomarkers is a main limitation for clinical diagnosis and treatment. The transient receptor potential (TRP) channels play important roles in the occurrence and development of tumors, which may have the potential as a therapeutic target for UVM. This current study aimed to identify the potential effect and function of the TRPs that could provide survival prediction and new insight into therapy for UVM. Based on the transcriptome data and potential key genes of UVM were screened using the Cancer Genome Atlas (TCGA) databases, Gene expression analysis showed the expression of TRPM4, TRPV2 and other TRPs was high levels in UVM. Using survival analysis, we screened out that the high expression of TRPM4 and TRPV2 was negatively correlated with the prognosis of UVM patients. Cox regression analysis and functional enrichment analysis further indicated that TRPM4 and TRPV2 were the most convincing therapeutic targets of UVM, and the majority of genes involved in ferroptosis pathways in UVM showed positively correlated with the expression levels of TRPM4 and TRPV2. In conclusion, TRPM4 and TRPV2 were considered as two novel prognostic biomarkers and a promising targeted therapy in UVM.

Retraction Notice to: Schizandrin A Protects Human Retinal Pigment Epithelial Cell Line ARPE-19 against HG-Induced Cell Injury by Regulation of miR-145.

[This retracts the article DOI: 10.1016/j.omtn.2019.10.026.].

Efficacy of Conversion to Aflibercept for Diabetic Macular Edema Previously Refractory to Bevacizumab or Ranibizumab: A Meta-analysis of High-Quality Nonrandomized Studies.

Background: Aflibercept has been widely used in treating diabetic macular edema (DME). However, the effect of aflibercept in treating DME refractory to bevacizumab or ranibizumab has not been well established. Objective: To assess the therapeutic effect of switching from bevacizumab or ranibizumab to aflibercept in the treatment of refractory DME. Methods: Relevant studies were searched from 3 databases: the Cochrane Library, PubMed, and Web of Science. Data on changes in best-corrected visual acuity (BCVA), central macular thickness (CMT), and adverse events within the follow-up period were collected and pooled using weighted mean differences (WMDs) with corresponding 95% CIs in a random effects model. The between-study heterogeneity was tested using the χ2 test and the I2 statistic, and funnel plots were used to evaluate the publication bias. Results: A total of 11 nonrandomized trials met the inclusion criteria and were included in the meta-analysis. Our studies showed significant improvements in the BCVA (WMD = 100.55; 95% CI = 68.46 to 132.63; P < 0.01) and reduction in CMT (WMD = 0.09; 95% CI = 0.03 to 0.14; P < 0.01) after switching to aflibercept. Although a large amount of heterogeneity was detected in the CMT results among these studies, the sensitivity analyses showed the reliability and stability of our results. Conclusion and Relevance: There were significant improvements in both visual and anatomical outcomes after switching from bevacizumab or ranibizumab to aflibercept, without risk of adverse events. Thus, switching therapy may be a safe and effective treatment for patients with refractory DME.

Schizandrin A Protects Human Retinal Pigment Epithelial Cell Line ARPE-19 against HG-Induced Cell Injury by Regulation of miR-145.

Diabetic retinopathy (DR) is a serious complication of diabetes, which is the main cause of blindness among adults. Traditional Chinese medicines (TCMs) have been proven to delay the development of DR. Nonetheless, the effect of Schizandrin A (SchA) on DR remains uninvestigated. The present study aimed to probe the protective effect of SchA on high-glucose (HG)-induced injury in ARPE-19 cells. We observed that SchA accelerated cell proliferation, prohibited apoptosis, and restrained pro-inflammatory cytokines (monocyte chemoattractant protein-1 [MCP-1], interleukin-6 [IL-6], and tumor necrosis factor alpha [TNF-α]) and reactive oxygen species (ROS) level in HG-stimulated cells. Additionally, miR-145 expression was upregulated in HG and SchA co-treated cells, and miR-145 inhibition reversed the protective effect of SchA on HG-managed ARPE-19 cells. Interestingly, downregulated myeloid differentiation factor 88 (MyD88) was found in HG and SchA co-treated cells, and upregulation of MyD88 was observed in miR-145 inhibitor-transfected cells. Additionally, SchA hindered nuclear factor κB (NF-κB) and p38 mitogen-activated protein kinase (p38MAPK) signaling pathways in HG-treated ARPE-19 cells. The findings validated that SchA could protect ARPE-19 cells from HG-induced cell injury by regulation of miR-145.

Effect of Pars Plana Vitrectomy With or Without Cataract Surgery in Patients with Diabetes: A Systematic Review and Meta-Analysis.

INTRODUCTION: Pars plana vitrectomy (PPV) is considered to be an essential and effective surgical approach for the management of complications of diabetic retinopathy. Given the high rate of accelerated cataract progression after PPV, PPV combined with cataract surgery appears to be an attractive treatment option for patients with diabetes. However, this combined surgical approach remains controversial in terms of effectiveness and safety. We have therefore conducted a meta-analysis to evaluate the treatment outcome of PPV with or without cataract surgery. METHODS: A systematic search of three electronic databases (PubMed, Web of Science, and the Cochrane Library) was performed to identify relevant articles, using the key words "pars plana vitrectomy," "cataract," and "diabetic retinopathy." Main outcome measures included the final visual acuity and postoperative complications. The incidence of postoperative complications was pooled using odds ratio (OR) with 95% confidence intervals in a random effect model. RESULTS: Ultimately, one randomized controlled trial (RCT) and four high-quality retrospective studies met the inclusion criteria and were included in the meta-analysis. In four of these studies, final visual acuity did not vary significantly between patients undergoing PPV alone and those undergoing PPV combined with cataract surgery (combined surgery). Only one study reported better visual improvement in the combined treatment group. Our analysis also showed that most phakic eyes after PPV had cataract progression with varying degrees. In addition, patients receiving PPV alone had a lower risk of neovascular glaucoma (OR 0.36; P < 0.05), iris synechias to anterior capsule (OR 0.36; P < 0.05), and iris rubeosis (OR 0.26; P < 0.05) compared with those receiving combined surgery. CONCLUSION: Overall, our findings show that PPV combined with cataract surgery achieved good outcomes without a substantial increased risk to visual acuity or most complications. Given the high rates of cataract progression after PPV, combined surgery may be the more appropriate treatment for patients with diabetes and coexistent visually significant cataract.

Salidroside alleviates high-glucose-induced injury in retinal pigment epithelial cell line ARPE-19 by down-regulation of miR-138.

Diabetic retinopathy (DR) is a complication of diabetes leading cause of blindness in adults. Salidroside (SAL) is a main ingredient from Rhodiola rosea L., has been reported to have a beneficial protection on vascular function. However, whether SAL is a suitable treatment for DR remains unreported. The study aimed to investigate the effect of SAL on high-glucose (HG)-induced injury in ARPE-19 cells. ARPE-19 cells were managed with diverse concentrations of glucose, and constructed a model of HG-induced ARPE-19 cells injury. Then, SAL was employed to stimulate ARPE-19 cells, and cell viability, apoptosis, apoptosis-associated factors, the pro-inflammatory cytokines, and ROS levels were determined. The correlation between miR-138 and SIRT1 was predicated by bioinformatics software of TargetScan (http://www.targetscan.org/) and Dual luciferase reporter assay. MiR-138 mimic, inhibitor and NCs were transfected into ARPE-19 cells, and the impacts of miR-138 on HG-induced cell injury were investigated. PI3K/AKT and AMPK signalling pathways were examined to explore the underlying mechanism. The results disclosed that HG inhibited cell viability, promoted apoptosis, up-regulated IL-6 and TNF-α, as well as increased ROS level in ARPE-19 cells. But, SAL obviously alleviated HG-induced ARPE-19 cells injury. Repressed miR-138 was triggered by SAL, and SIRT1 was predicated as a direct target of miR-138. Overexpressed miR-138 declined the protective effect of SAL on HG-injured ARPE-19 cells. Besides, SAL activated PI3K/AKT and AMPK pathways by adjusting miR-138. In conclusions, SAL flattened HG-induced injury in ARPE-19 cells by repression of miR-138 and activating PI3K/AKT and AMPK pathways.

Facile synthetic Photoluminescent Graphene Quantum dots encapsulated ß-cyclodextrin drug carrier system for the management of macular degeneration: Detailed analytical and biological investigations.

Drug administration by effective nano-carriers is an emerging and growing technology in the field of bio-medicine and particularly Age -related macular degeneration (AMD). This developed nanomaterials based methods with drug administration maximizes the biocompatibility and systemically increases drug delivery profile for the drugs. Herein, we described the effective drug molecules delivery profiles by the hydrothermally synthesized graphene quantum dots (GQDs) encapsulated with supramolecular ß-cyclodextrin (ß-CD) as a drug delivery system for AMD. The drug release profiles were analysed and plotted by two different types of drugs ((Bevacizumab (Bev) and Ranibizumab (Ran))) and compounds displayed an initial burst delivery percentage of 55.7 ±â€¯1.6% and 52.2 ±â€¯2.6, respectively, within 15 min. After 1 h, 94.2% (Ran) and 93.1% (Bev) of loaded drug molecules were released from the ß-CD encapsulated GQDs in sustained manner. The biocompatibility of the synthesized carriers was investigated quantitatively and qualitatively with the mouse Fibroblast L929 cell line. The biological cell analysis observed by calculated cell count and green fluorescence visualization has been clearly confirmed the samples are non-toxic and highly compatible to the cells with more than 90% cell viability after 5 days cell culture. The observed material properties and biological results demonstrated that the suitability of the developed nano-carriers for the drug delivery system in the AMD.

Effect of Intravitreal Bevacizumab with or without Macular Photocoagulation for Diabetic Macular Edema: A Meta-Analysis.

INTRODUCTION: In this meta-analysis, we aimed to assess the possible benefits of macular photocoagulation (MPC) as an additional treatment with intravitreal bevacizumab (IVB) in patients with diabetic macular edema. METHODS: The studies were identified from three databases: PubMed, Web of Science, and the Cochrane Library. The main outcome measures included change in best-corrected visual acuity (BCVA), differences in central macular thickness (CMT), and adverse events within the follow-up period. The results were pooled using weight mean difference with their corresponding 95% confidence intervals. A fixed or random effects model was employed, depending on the heterogeneity of the inclusion trials. RESULTS: Finally, three randomized controlled trial and two high-quality retrospective studies were identified and included. Changes in CMT at 1, 3, and 6 months did not vary significantly between the IVB-alone group and the IVB with MPC group (P = 0.26, 0.06, and 0.65, respectively). Similarly, changes in BCVA at 1, 3, and 6 months also did not vary significantly between the two groups (P = 0.20, 0.91, and 0.70, respectively). Whereas substantial heterogeneity was detected in the CMT results among these studies, the sensitivity analyses showed Solaiman's study was probably the source of the heterogeneity. No publication bias was detected by funnel plots in this study. CONCLUSION: Results of this meta-analysis showed that the treatments with IVB alone and combined IVB and MPC were similarly effective in improving BCVA and reducing CMT. However, more evidence is needed to evaluate their effects in the long-term periods.

Correlation of MMP-9, GA, HbA1c, and adipokines levels with DR / 国际眼科杂志(Guoji Yanke Zazhi)

·AIM: To investigate the correlation of matrix metalloproteinase -9 (MMP-9), glycated albumin (GA), glycosylated hemoglobin ( HbA1c ) and adipokines ( including visfatin, resistin and leptin ) with diabetic retinopathy ( DR) .·METHODS:From March 2015 to March 2017, 74 patients with DR were treated in our hospital, including 40 patients ( 80 eyes ) with non proliferative diabetic retinopathy ( NPDR ) and 34 patients ( 68 eyes ) with proliferative diabetic retinopathy ( PDR ) , and diabetes mellitus 40 patients ( 80 eyes ) with non DR ( NDR ) and 40 healthy volunteers (80 eyes) were selected as controls, the levels of MMP-9, GA, HbA1c, visfatin, resistin and leptin in each group were detected.·RESULTS: PDR group visfatin was 4. 41 ± 0. 82ng/mL, was significantly lower than the NPDR group, NDR group and control group ( P<0. 05 ) , while, resistin, leptin and MMP- 9 were 9. 01 ± 1. 04ng/mL, 17. 96 ± 2. 03μg/L and 740. 06 ± 84. 43μg/L, GA and HbA1c were 26. 14%± 4. 57%and 17. 60% ± 1. 91%, significantly higher than those of NPDR group, NDR group and control group ( P<0. 05 ) . NPDR group visfatin was 6. 44 ± 0. 79ng/mL, was significantly lower than that of NDR group and control group (P<0. 05), while, resistin, leptin and MMP-9 were 7. 80±0. 87ng/ml, 15. 68±1. 98μg/L and 634. 12±80. 22μg/L,GA and HbA1c were 22. 06%± 4. 38% and 12. 46%± 1. 69%, significantly higher than those of NDR group and control group (P<0. 05). MMP-9, GA, HbA1c were positively with DR levels ( rs = 0. 523, 0. 461 and 0. 414, P<0. 05 );visfatin was negatively correlated with DR levels ( rs = -0. 433, P < 0. 05 ), resistin and leptin were positively correlated with DR levels (rs=0. 401 and 0. 460, P<0. 05).·CONCLUSION: MMP-9, GA, HbA1c, and adipokines may play a role in the development and progression of DR, in which MMP-9 is associated with adipokines, both are not significantly related to the levels of GA and HbA1c.

The distribution of Mn2+ in rabbit eyes after topical administration for manganese-enhanced MRI.

PURPOSE: To analyze the distribution of Mn(2+) in rabbit eyes after topical administration of Mncl2 for manganese-enhanced MRI. METHODS: Forty-eight Chinese white rabbits were divided into three groups. In group 1 (n = 4), the baseline concentration of Mn(2+) in aqueous, vitreous and serum samples were analyzed. In group 2 and 3, the rabbits received one topical instillation (20 µL) of Mncl2 (1 mol • L(-1)). In group 2 (n = 40), aqueous, vitreous and serum samples were collected and analyzed at predetermined time points (0.5, 1, 2, 4, 6, 12, 24, 48, 72 and 168 hours postdose). Assays were performed using inductively coupled plasma-mass spectrometer (ICP-MS). In group 3 (n = 4), after topical administration of Mncl2, dynamic manganese-enhanced MRI (MEMRI) was performed at predetermined time points. The signal-to-noise ratio (SNR) was calculated to evaluate the enhancements of eyes. RESULTS: After topical administration, the maximum concentrations of Mn(2+) in the aqueous and vitreous samples were 11.1641 ± 0.7202 (2 hours) and 1.5622 ± 0.1567 (12 hours). In group 3, the maximum enhancement of aqueous humor (SNR = 108.81 ± 10.65) appeared at 2 hours postdose, whereas, no significant changes were detected in vitreous. CONCLUSION: Mn(2+) could distribute into aqueous humor rapidly after topical administration of Mncl2, whereas, the concentration of Mn(2+) in vitreous body fluctuated in a narrow range over the course. The uptake of Mn(2+) in retina may involve several different pathways.

Removal of a giant nonmagnetic intraocular foreign body using micro alligator forceps.

PURPOSE: To introduce a new method for removal of a giant nonmagnetic intraocular foreign body using micro alligator forceps. PATIENTS AND METHODS: Eleven patients underwent pars plana vitrectomy and lensectomy. The micro alligator forceps were used to grasp and extract the giant nonmagnetic intraocular foreign body through a sclerocorneal tunnel. RESULTS: All patients underwent surgical removal of the intraocular foreign body successfully without any intraoperative complications. The alligator forceps were operational in the intraocular environment and effective in surgical maneuvers. There was no accidental slippage during the procedures. CONCLUSION: Micro alligator forceps are a feasible option for removal of giant nonmagnetic intraocular foreign body during vitreoretinal surgery and offer advances in terms of operating stability and surgical safety.