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Purpose Myopic foveoschisis occurs in 9-34% of highly myopic eyes with posterior staphyloma. The pathogenesis is still not fully understood. But the relative inflexibility of the inner retina and a tangential traction induced inward traction force in the posterior staphyloma are possible mechanisms. Conventional internal limiting membrane ( ILM) peeling generally yields good results. However, a postoperative full-thickness macular hole happens in 13-28% of cases. Therefore, this study describes a modified ILM peeling technique named ' ILM maculorrhexis' to minimize the occurrence of postoperative macular hole in patients with foveoschisis. Methods This retrospective case review that included 10 eyes of 10 consecutive patients who underwent vitrectomy with ILM maculorrhexis to treat myopic foveoschisis was studied. After surgery, complete ophthalmic examination and SD-optic coherence tomographic examinations were performed 1, 3, 6, 9 and 12 months postoperatively. Results After surgical intervention, the foveoschisis resolved dramatically in all 10 eyes. The mean central foveal thickness decreased significantly from 840 μ to 273 μ at 12 months postoperatively. Mean Log MAR best-corrected visual acuity improved from 1.04 preoperatively to 0.59 12 months postoperatively. After the follow-up time of at least 12 months, all 10 eyes remained fovea attached, and none of the 10 eyes developed macular hole. Conclusions This technique minimizes traction force over the extremely thinned foveal tissue in highly myopic eyes. In the long-term follow-up of at least 12 months, all 10 cases had good anatomic and visual results. But we still need a larger case number and longer follow-up for further evaluation. [ABSTRACT FROM AUTHOR]

Image authentication, which is provided with capabilities of tamper detection and data recovery, is an efficient way to protect the contents of digital images. Vector quantization (VQ) is a data compression method. A VQ-compressed code is not only a significant image authentication feature but also applicable in restoring possibly damaged pixels. However, if an image is tampered with, the necessary recovery information disappears. To solve this problem, this paper proposes a quantization-based image authentication scheme using two-dimensional (2D) barcodes to protect important features. Compared with older linear barcodes, 2D barcodes are a machine-readable representation of binary data that possess capabilities of location and tolerance. This paper presents a method for incorporating VQ-compressed code into 2D barcodes and embedding those barcodes into the image itself. Experimental results showed that VQ codes can be completely reserved during data recovery even though quick response codes sustain certain perceptible distortions. Moreover, the proposed scheme provided higher quality authenticated and recovered images compared with previous methods. [ABSTRACT FROM AUTHOR]

Image authentication is a type of technique for the content protection of digital images. This technique is able to detect and locate tampered regions on a digital image. In this paper, two self-embedding image authentication approaches are proposed to involve distinctive singular values. Both of them extract self-characteristics of an image as the crucial authentication information for that image. Subsequently, this information is converted into the two dimensional code format and that codes are then embedded into digital image pixels. With the capability of error correction in two dimensional codes, the extracted authentication data, even being detected with a tamper, still can be completely restored and errorless. As well, it can be utilized to detect whether an image has been tampered with or not. According to experimental results, the proposed approaches are superior to other schemes for images that have been modified to a certain attack extent because the authentication data could be completely extracted in more effective way, and the tampered regions could be identified more accurately. In addition, the proposed approaches utilize these complete self-characteristics to restore tampered regions into their original states. [ABSTRACT FROM AUTHOR]

Aim To develop or enhance the job satisfaction and organisational commitment of nurses by implementing job rotation and internal marketing practices. Background No studies in the nursing management literature have addressed the integrated relationships among job rotation, internal marketing, job satisfaction and organisational commitment. Method This cross-sectional study included 266 registered nurses (response rate 81.8%) in two southern Taiwan hospitals. Software used for data analysis were spss 14.0 and amos 14.0 (structural equation modelling). Results Job rotation and internal marketing positively affect the job satisfaction and organisational commitment of nurses, and their job satisfaction positively affects their organisational commitment. Conclusion Job rotation and internal marketing are effective strategies for improving nursing workforce utilisation in health-care organisations because they help to achieve the ultimate goals of increasing the job satisfaction of nurses and encouraging them to continue working in the field. This in turn limits the vicious cycle of high turnover and low morale in organisations, which wastes valuable human resources. Implications for nursing management Job rotation and internal marketing help nursing personnel acquire knowledge, skills and insights while simultaneously improving their job satisfaction and organisational commitment. [ABSTRACT FROM AUTHOR]

Objective The study aimed to determine a practical strategy for differentiating between autoimmune pancreatitis ( AIP) and pancreatic malignancy in order to avoid unnecessary surgical resection. Methods Altogether, 19 patients with AIP or other pancreatic diseases underwent routine examinations including liver function test and carbohydrate antigen 19-9, computed tomography and/or magnetic resonance imaging. Serum immunoglobulin G ( IgG) and/or IgG4 was determined in patients with clinically suspected or pathologically proven AIP. Patients with suspected AIP either received diagnostic steroid therapy or laparotomy (if malignant tumors could not be excluded). Surgery was not performed in patients with a definite diagnosis of AIP by fast intraoperative frozen biopsy. Those with confirmed AIP received steroid treatment. Results In total, 15 cases were finally confirmed as AIP with eight diagnosed preoperatively, five confirmed by surgical pathology (preoperatively misdiagnosed) and two by intraoperative biopsy. Of these 15 patients with AIP and one without AIP, 14 had elevated serum γ-globulin levels. It was proven by subsequent antibody tests that serum IgG or IgG4 were simultaneously increased. Conclusions Elevated serum γ-globulin level can be used as a preoperative sentinel indicator for differentiating between IgG4-related AIP and pancreatic malignancy. Serum IgG or IgG4 tests should be further performed in those with elevated serum γ-globulin level, which helps to identify AIP in order to avoid unnecessary operation. [ABSTRACT FROM AUTHOR]

Abstract: Statins, inhibitors of 3-hydroxy-3-methylglutaryl-coenzye A reductase, possess pleiotropic effects that have been extended to modulation of various cellular behaviors. This study aimed at examining whether atorvastatin (AVN) modulates cell growth, adhesion, migration, and contraction of cultured human retinal pigment epithelium (RPE) cells. The in vitro effects of AVN on human RPE cells was analyzed in terms of cell proliferation, cell cycle, cell adhesion, migration, and contraction assays. The modulatory effect of AVN on TGF-β2-triggered signaling was determined by Western blotting detection. AVN at submicromolar dose exhibited no prominent morphological alteration and cytotoxicity, whereas it elicited cytostatic effect at concentrations higher than 1 μM. Cell cycle analysis showed that AVN induced growth arrest in both G1 and G2/M phases. AVN at 1 μM or higher concentrations significantly suppressed RPE cell adhesion. Cell migration and 3D collagen contraction assays showed that AVN significantly suppressed RPE cell migration and contractility, respectively. Mechanistically, AVN treatment transiently up-regulated phosphorylation of Akt, ERK1/2, and p38 MAPK, whereas down-regulated that of JNK1. Intriguingly, AVN pretreatment prominently attenuated the TGF-β2-mediated non-Smad signaling, including Akt, ERK1/2, p38 MAPK, and JNK1 phosphorylation. Besides, it directly reduced constitutive level of myosin regulatory light chain peptide MYL9 and mitigated the TGF-β2-induced phosphorylation of myosin phosphatase-targeting subunit 1, MYPT1. These in vitro findings strongly suggest that AVN possesses pleiotropic function on RPE cells, including anti-proliferation, anti-adhesion, anti-migration as well as anti-contraction. In conclusion, AVN treatment may be considered a useful therapy for proliferative vitreoretinal diseases. [Copyright &y& Elsevier]

Abstract: Geldanamycin (GA), a benzoquinone ansamycin, was originally isolated as a natural product with anti-fungal activity. GA and its analogs, including 17-allylamino-demethoxy geldanamycin (17-AAG), are also known to block the function of a molecular chaperone, heat shock protein 90 (Hsp90). In light of their anti-tumor properties through direct cytotoxicity and anti-angiogenicity, GA has been previously demonstrated to suppress hypoxia-induced VEGF production in retinal pigment epithelium (RPE) cells, implicating its applicability in treating intraocular neovascularization. This study aimed at investigating the effectiveness of Hsp90 inhibitor treatment in suppressing proliferation of cultured human RPE cells and elucidating its underlying mechanism. Cultured RPE cells were treated with GA or 17-AAG and subjected for cell proliferation assay and cell cycle analysis. Expression of apoptotic regulators and survival signaling activity were monitored by Western blotting. The results showed that both GA and 17-AAG significantly inhibited RPE cell proliferation at micromolar levels. Treatment with GA and 17-AAG led to growth arrests in G1 and S phases, increased sub-G1 hypodipoid cell population, induced apoptotic cell death, and upregulated P53 and P21 expression, although the drug-induced Bcl-2 upregulation cannot prevent cell death. Additionally, GA and 17-AAG significantly suppressed constitutive contents of phosphorylated ERK1/2 and total Akt proteins, and completely abrogated wortmannin-sensitized Akt phosphorylation. In conclusion, GA and 17-AAG inhibit RPE cell proliferation and induce cytotoxicity, possibly through downregulating Akt- and ERK1/2-mediated signaling activities. They might potentially constitute a therapeutic agent for ocular disorders with RPE over proliferation, such as proliferative vitreoretinopathy. [Copyright &y& Elsevier]

Abstract: Hypoxia is the most common factor contributing to the pathogenesis of choroidal neovascularization, which is the major cause for blindness and occurs in proliferative diabetic retinopathy and age-related macular degeneration. The purpose of this study is to investigate the role of retinal pigment epithelial (RPE) cells in the regulation of subretinal neovascularization under hypoxia and the possible function of a heat shock protein 90 (HSP90) inhibitor, geldanamycin (GA), in the regulation of VEGF expression. An in vitro hypoxic experimental model was used to mimic the ischemic microenvironment of RPE cells. The cell growth was measured by proliferation assay and the morphological observation was documented by microscope. The gene expression of VEGF, hsp70, hsp90α and hsp90β were measured using semi-quantitative RT-PCR. The VEGF release from RPE cells were detected by ELISA. No alteration in growth rate and cell morphology under 1% O2 condition for 24h was noticed. The proangiogenic growth factor VEGF, but not bFGF, released from hypoxia-treated cells were significantly higher than those of normoxic controls. A similar tendency of VEGF165 isoform gene expression, detected by RT-PCR, was noticed in hypoxia-treated cells. Heat shock pretreatment elevated hsp70 and VEGF165 gene expression and augmented the hypoxia-induced VEGF gene expression and protein release. Pretreatment with GA can significantly suppress the hypoxia-induced VEGF gene expression in and peptide release from RPE cells. These in vitro findings suggest that HSP90 inhibitors could be considered as novel anti-angiogenesis agents for diseases with intraocular neovascularization. [Copyright &y& Elsevier]

Abstract: This paper proposes a reversible data embedding scheme based on a VQ image compression technique which emphasizes that the original VQ compressed codes can be recovered after data extraction. In this proposed scheme, a VQ codebook, which had already been clustered into three groups, was adopted to achieve secret concealment and data recovery. In order to embed more secret data, the concepts of frequency clustering and trio extension were also introduced. Experimental results showed that the proposed scheme with the lossless recovery facility could work well. [Copyright &y& Elsevier]

It has been reported that retinoic acid (RA) may inhibit the growth of RPE and be used in the treatment of proliferative vitreoretinopathy (PVR). However, previous reports in this field have been conflicting. The main reason for these contradictory findings is that different methods for evaluating the effects of RA on RPE from different species have been used. In human specimens, only RPE from the donor eye (stationary) but not RPE from the PVR membrane (already at active proliferation status) have been tested. This study tested the effects of RA on the growth of RPE using a novel in vitro model: RPE from the PVR membranes, which simulates the in vivo situation of PVR patients better than RPE from the donor eyes. This study also used various methods to solve the conflicting results reported previously. We found that both all transretinoic acid (all-RA) and 13-cis-retinoic acid (cis-RA) can promptly (though not completely) inhibit proliferation of RPE (inhibition rate of 89%-90%) over a very wide range of concentrations (10-9-10-5 M) and various lengths of periods (2-12 days) in a dosedependent and time-dependent manner and without evident cytotoxic effects. Previously reported disadvantages discovered from the study of RPE from donor eyes, e.g., the absence of inhibitory effects on the early passages of cultured cells and inhibition occurring only after long-term treatment, do not present in RPE cells from the PVR membrane. The proliferation of RPE recovered from the inhibition by RA rapidly after the discontinuation of treatment, indicating that a continuous supply of the drug over a long period, i.e., until the breakdown of the blood-retinal barrier has been repaired, is essential for the success of drug treatment of PVR. [ABSTRACT FROM AUTHOR]

It has been well documented that RPE cells play an important role in the formation of proliferative vitreoretinopathy (PVR). We studied the effects of four most widely used anti-proliferative drugs, i.e., 5-fluorouracil (5-FU), daunomycin (DM), mitomycin C (MMC) and dexamethasone (DEX) in an in vitro model system (cultured human RPE). The cells treated with indicated concentrations of drugs for 48 h were harvested for DNA content analysis. In addition, a time course study with constant dosage of drugs was performed. The results revealed that, after incubation for 48 h, an increased percentage (31.1%) of S phase cells was noted with exposure to MMC (10 ng/ml). It was confirmed by 5-bromodeoxyuridine (BrdU) incorporation test that this increase does not result from higher transition rate from G1 to S phase. The cells of G2/M phase markedly increased from 13.8% to 29.7% with 10 ng/ml DM. We also demonstrated that 5-FU and MMC treatment led to cell accumulation at S phase and DM treatment resulted in cell accumulation at G2/M phase, These findings were compatible with their pharmacological mechanisms. Development of an in vitro model using cultured human RPE to study the effects of various anti-proliferative drugs on cell cycle can provide a rapid, safe and inexpensive method for selection of drugs used for management of PVR. [ABSTRACT FROM AUTHOR]

The effects of various antiproliferative drugs have been tested in numerous cell types in vitro, but a comparison of effects of these drugs on cultured human retinal pigment epithelium (RPE) has not been reported. We studied the effects of four most widely used antiproliferative drugs (5-FU, daunomycin, mitomycin and dexamethasone) in a new in vitro model system (cultured human RPE). Various concentrations and exposure periods were tested in four human RPE cell lines. 5-FU showed a dose-dependant growth inhibition, with an ID[sub 50] of 5.35 ± 2.38 × 10[sup -7] M after 4 days culture. A decrease of cell number occurred relatively later, the slope of the dose-response curve was less steep than that of others. Mitomycin C showed an immediate and strong growth inhibition and cytotoxic effects, with an ID[sub 50] of 3.73 ± 0.71 × 10[sup -9] M. RPE cultured with daunomycin showed an abrupt decrease of cell number from 10[sup -9] M to 10[sup -8] M, the ID value was 1.07 ± 0.23 × 10[sup -8] M. Dexamethasone showed a biphasic effect; it stimulated cell growth at 10[sup -7] to 10[sup -6] M and inhibited cell growth at 10[sup -4] M or higher, with an ID[sub 50] of 6.05 ± 1.61 × 10[sup -3] M. The advantages and disadvantages of these drugs and the prospective clinical application of these drugs for management of proliferative vitreoretinopathy (PVR) were discussed. Development of an in vitro model using cultured human RPE to study the effects of various antiproliferative drugs can provide a rapid, safe and inexpensive method for selection of drugs used for management of proliferative vitreoretinopathy. [ABSTRACT FROM AUTHOR]

The incidence of recurrent vitreous hemorrhage of proliferative diabetic retinopathy following posterior vitrectomy ranges from 29% to 75% in reported series. Fluid-gas exchange and vitreous cavity lavage are the popular methods of treating this kind of recurrent hemorrhage. The fluid-gas exchange cannot offer clear vision immediately after the procedure. To improve the function of the classic vitreous cavity lavage, we designed a volume homeostatic fluid-fluid exchanger - Chen's I/A device. Tissue plasminogen activator (t-PA) is a protease that preferentially converts fibrin-bound plasminogen to the active proteolytic enzyme, plasmin. It has been clinically and experimentally proven effective in lysis of postvitrectomy blood clot and fibrin formation. When the blood clot is formed in the vitreous cavity, intravitreal injection of t-PA can convert plasminogen to plasmin and remove the clot. From July 1999 to January 2000, ten eyes of postvitrectomy diabetic vitreous hemorrhage (PDVH) were collected. In each case, 4 days after intravitreal injection (IVI) of t-PA (30 μg), vitreous cavity lavage was performed with Chen's I/A device. Of these cases, 8 eyes (80%) experienced an immediate clearing of the vitreous cavity. Early complications included anterior hyaloid fibrovascular proliferation (2 eyes) and postoperative intraocular pressure elevation (3 eyes). On the basis of the results of this study, our conclusion is that volume homeostatic vitreous cavity lavage, combined with intravitreal injection of t-PA, is an excellent method for treatment of postvitrectomy diabetic vitreous hemorrhage but, in cases of PDVH with iris rubeosis, the advantage of this procedure is uncertain. [ABSTRACT FROM AUTHOR]

This is an observational study of fluorescein angiography (FA) in consecutive patients with rhegmatogenous retinal detachment (RRD) in Changhua Christian Hospital to investigate the peripheral retinal vascular patterns in those patients. All patients had their age, sex, axial length (AXL), and refraction status (RF) recorded. According to the findings in FA of the peripheral retina, the eyes were divided into 4 groups: in group 1, there was a ramified pattern of peripheral retinal vasculature with gradual tapering; in group 2, there was an abrupt ending of peripheral vasculature with peripheral non-perfusion; in group 3, there was a curving route of peripheral vasculature forming vascular arcades or anastomosis; and in group 4, the same as in group 3, but with one or more wedge-shaped avascular notches. Comparisons of age, sex, AXL, and RF, association of breaks with lattice degeneration and retinal non-perfusion, surgical procedures utilized, and mean numbers of operations were made among the four groups. Of the 73 eyes studied, there were 13 eyes (17.8%) in group 1, 3 eyes (4.1%) in group 2, 40 eyes (54.8%) in group 3 and 17 eyes (23.3%) in group 4. Significant differences in age, AXL and RF, and association of retinal breaks to non-perfusion were noted among the four groups. Patients in group 1 had older ages, while younger ages were noted in groups 3 and 4. Eyes in group 1 had the shortest average AXL and were least myopic in contrast to the eyes in groups 3 and 4. Association of retinal breaks and retinal non-perfusion was significantly higher in groups 2, 3 and 4 than in group 1. In conclusion, peripheral vascular anomalies are common in cases with RRD. Patients with peripheral non-perfusion tend to be younger, with longer axial length and have the breaks associated with retinal non-perfusion. [ABSTRACT FROM AUTHOR]

Purpose. To evaluate the long-term anatomic and functional outcomes of autologous neurosensory retinal free flap transplantation (ART) for patients with refractory large macular hole (MH). Design. Retrospective interventional case series. Methods. We reviewed 9 patients who underwent ART for their refractory large MH. In this extended follow-up study, postoperative assessment including spectral-domain optical coherence tomography and best-corrected visual acuity (BCVA) were recorded at 12, 15, 18, 21, and 24 months after surgery. Results. The macular hole of all patients appeared successfully closed during the whole follow-up period. The mean logMAR BCVA improved from 1.61 ± 0.44 (preoperative) to 0.72 ± 0.30 (12 months after surgery) (p < 0.001). Thereafter, the mean BCVA remained stable at each follow-up. At the mean 16.0 ± 0.8 months postoperatively, inner retinal cystic changes were observed in 4 eyes (44.4%), but these did not significantly affect vision. Conclusion. ART is a good alternative technique for closing large refractory macular holes. Although inner retinal cystic changes were observed in 4 eyes (44.4%), this phenomenon did not significantly affect visual acuity. It provides long-term good anatomical and functional results, especially in cases where insufficient ILM or lens capsule are left. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to investigate the effect of three consecutive intravitreal bevacizumab injections (IVB) on long-term outcome for patients with macular edema after epiretinal membrane (ERM) removal. Methods: All patients in both the treatment and control groups had persistent macular edema 3 months after ERM removal. The patients in the treatment group received three consecutive IVB in an interval of approximately 4 weeks. The main outcome measures included logarithm of the minimum angle of resolution (logMAR) best-corrected visual acuity (BCVA) and central foveal thickness (CFT) determined by optical coherence tomography. Results: Two weeks after the first IVB, CFT decreased significantly by 24.1 ± 4.2 μm in the treatment group versus 4.2 ± 2.1 μm in the control group (p < 0.001). However, the mean reduction in CFT after 12 months did not differ significantly between the two groups (35.2 ± 4.9 vs. 33.7 ± 4.6 μm, p = 0.824). No significant differences were found for logMAR BCVA between the two groups at each follow-up. Conclusion: IVB could significantly decrease macular edema 2 months after the initial injection but failed to make significant differences in final CFT and logMAR BCVA. [ABSTRACT FROM AUTHOR]

Abstract: Information hiding methods are currently exploited by many researchers for various applications. Proposing an efficient and feasible information hiding method is valuable. This paper presents a new reversible information hiding method for vector quantization (VQ)-compressed grayscale images by using joint neighboring coding (JNC) technique. The proposed method embeds secret data by using the difference values between the current VQ-compressed index and left or upper neighboring indices. The experimental results show that the proposed method achieves the best visual quality of reconstructed images compared with the two related works. In addition, the proposed method obtains as high embedding capacity as Lin and Chang''s method, followed by Yang et al.''s method. As for execution speed, Yang et al.''s method is fastest, followed by the proposed method, and then Lin and Chang''s method. With respect to bit rate, the proposed method has a little higher bit rate in comparison with the two related works. [Copyright &y& Elsevier]

Purpose: To determine whether postoperative oral 13-cis-retinoic acid (RA) treatment could improve the outcome of vitreoretinal surgery with silicone oil for the management of proliferative vitreoretinopathy (PVR). Design: Prospective controlled randomized interventional case series. Methods: This study included 35 eyes of 35 patients with primary rhegmatogenous retinal detachment and PVR. All patients underwent surgical repair by similar procedures. The RA group consisted of 16 patients who received 10 mg oral RA twice daily for eight weeks postoperatively. The control group included 19 patients without taking RA. The outcome measure included the rate of retinal attachment, macular pucker formation, ambulatory vision, and RA–related side effects. Results: At last follow-up (at least one year postoperatively), 15 of 16 eyes (93.8%) in the RA group and 12 of 19 eyes (63.2%) in the control group maintained retinal attachment (P = .047). The rate of macular pucker formation was significantly lower in the RA group (18.8% vs 78.9% in the control group; P = .001). A higher rate of ambulatory vision was achieved in the RA group as compared to the control group (56.3% vs 10.5%; P = .009). Conclusions: Postoperative administration with oral moderate dosage of RA for eight weeks appears to maintain retinal attachment, decrease the macular pucker, and improve vision after surgical repair for eyes with PVR. [Copyright &y& Elsevier]

The aim of this study was to evaluate the effects of indocyanine green (ICG), which is a fluorescent dye recently used for staining during manipulation of the internal limiting membrane (ILM) in surgery, on cultured human retinal pigment epithelial (HRPE) cells. Different concentrations, up to 0.25% (weight/volume), of ICG were added to the culture medium, which contained the cultured human RPE cells. Then the cell-growth curve and cell viability were assayed with a direct cell count and MTS cell proliferation kit, respectively. Two (2) models of experimentations, a dose-response group and a short-term application group, were designed. We obtained data for IC50 values for 24-, 48-, and 72hour ICG treatments, which were 0.062%, 0.041%, and 0.035%, respectively. This implies that the longer the culture duration, the lower the concentration of ICG, which can inhibit the HRPE cells. In the group of 3-day sequential incubations with ICG treatment, a 0.01% concentration significantly inhibited HRPE growth. In addition, HRPE cells were damaged immediately after ICG treatment, and the damage was ICG dose-related. In the sequential 3-day incubation, compared to the control group, the surviving HRPE cells of each treated group had the same growth rate. In conclusion, ICG has a relatively toxic effect on cultured HRPE cells, even in much lower concentrations than clinical nondilution status (0.25%). Since an ICG toxic effect on HRPE cells was found in our study (in vitro), we highly recommend staining the ILM with as low a concentration of ICG as possible, and washing out the residual intravitreal ICG as thoroughly as possible after finishing the peeling of the ILM. [ABSTRACT FROM AUTHOR]

Background: To compare refractive outcomes after phacoemulsification and toric IOL implantation using two different toric calculators for initial astigmatism assessment in a real-world setting. Methods: This was a retrospective, comparative, interventional case series. Patients over 30-year-old who underwent phacoemulsification and toric IOL implantation (AcrySof® Toric IOL) by the same surgeon between 2017 and 2018 were included. Eyes with irregular astigmatism, previous corneal refractive surgery, intraocular surgery, corneal pathology, macular pathology and pupil abnormalities were excluded. IOL toricity was determined by using a calculator provided by the AcrySof Toric calculator before 2018 and Barrett Toric Calculator after 2018. Patient demographics, corneal topography, vector and preoperative and postoperative refraction were collected and analyzed at three months postoperative. Results: Thirty-two eyes of 32 patients were included in the final analysis. 0.1D for surgically induced astigmatism was used. Group 1 included 14 eyes assessed with the original (AcrySof) toric IOL calculator, and group 2 included 18 eyes assessed with the Barrett toric IOL calculator. In group 1, postoperative astigmatism less than − 1.00D, − 0.75 D, and − 0.5D was achieved in 88.2%, 76.1% and 53.7% of eyes, respectively, while, in group 2, 89% eyes achieved postoperative residual astigmatism less than 0.5D and all eyes achieved postoperative residual astigmatism less than 0.75D. The proportion of patients with lower postoperative astigmatism was significantly higher in Group 2 (p< 0.05 by chi-square test), a pattern that still held when we divided patients into multiple groups. Vector analysis with the Alpins methods also supported better outcomes in the Barrett group (0.71 D vs 0.35 D). Conclusion: The Barrett Toric calculator resulted in better results in the prediction of residual astigmatism than original (AcrySof) toric calculators. [ABSTRACT FROM AUTHOR]

Background: To evaluate the efficacy of micro-incision vitrectomy surgery using a non-contact wide-angle viewing system for fovea-attached type epiretinal membrane, and to report the factors influencing the outcome. Methods: A retrospective, comparative case series that included 50 patients with fovea-attached type epiretinal membrane who received micro-incision vitrectomy surgery using a non-contact wide-angle viewing system. Results: All patients were followed-up for a minimum of 12 months. Seven cases were classified as group 1A (mainly outer retinal thickening), 17 were group 1B (more tenting of outer retina and distorted inner retina), and 26 were group 1C (prominent inner retina thickening and inward tenting of outer retina). Outcome measures included operation time, recurrent rate, postoperative BCVA, and CRT. The mean operative time was 26.2 minutes. The mean change of BCVA (LogMAR) was − 0.43 (p< 0.001). The mean change of CRT was 135.3 μm (p< 0.001). The mean change of CRT was significantly higher in group 1C. Worse preoperative BCVA, male gender, and longer operative time can predict better postoperative BCVA found by multivariate logistic regression and multiple regression models. Conclusion: Significant improvement in BCVA and CRT is noted after micro-incision vitrectomy surgery to operate fovea-attached type epiretinal membranes. Worse preoperative BCVA, male, and longer operation time could predict better improvement. These findings may assist surgeons in better evaluating the potential of this method to help their patients with epiretinal membranes. [ABSTRACT FROM AUTHOR]

Diabetic macular edema (DME) is the most common cause of vision loss among patients with diabetes mellitus (DM), rendering it an important growing challenge in ophthalmology. In the past decades, the management strategies for DME had a few paradigm shifts, and the advent of an expanding number of anti-vascular endothelial growth factor (VEGF) agents also calls for an in-depth examination of the currently available evidence. This article was composed with the intention to provide recommendations for practicing clinicians to improve the management and, through it the outcomes of DME. Drawing from current guideline recommendations, clinical trial findings and local clinical experiences, these consensus recommendations for the management of DME were formed by an expert panel through iterations of discussion and voting. First, the treatment goal of DME is to achieve best visual outcome with edema improvement while minimizing treatment burden. Second, anti-VEGF therapy should be considered as the first-line treatment for patients with center-involving DME causing vision loss. Baseline visual acuity (VA) and central subfield thickness (CST) should be taken into consideration when choosing anti-VEGF agents. Third, early intensive anti-VEGF therapy (at least 3 monthly doses) is important for better patients' VA and anatomical improvement. In non-responders who have already been treated with 3-5 injections of anti-VEGF agents, it is reasonable to switch to other modalities, such as steroids. Finally, for the follow-up phase, fixed or individualized dosing should be considered based on VA and OCT. [ABSTRACT FROM AUTHOR]

Purpose. To investigate the functional and anatomical outcome of the 0.7 mg dexamethasone (Ozurdex) intravitreal implant (IVD) in eyes with long-term macular edema after macular epiretinal membrane removal. Methods. We enrolled 40 eyes with persistent macular edema at least 12 months after epiretinal membrane removal. Twenty eyes in the IVD group received IVD and the other 20 eyes were in the control group. The main outcome measures were change in best-corrected visual acuity (BCVA) and central foveal thickness (CFT). Results. For eyes in the IVD group, the mean BCVA improved by 3.45 lines to 0.47 logMAR one month after IVD. However, the mean BCVA improved by only 0.14 lines to 0.74 logMAR at the same time in eyes in the control group. Six months later, the mean BCVA improved to 0.31 and 0.74 logMAR in the IVD and control groups, respectively. In the IVD group, the mean CFT decreased rapidly by 116.8 μm to 333.9 μm one month after IVD. Thereafter the CFT decreased at a slower pace. In the control group, the CFT remained static during the follow-up period. However, in the IVD group, 6 months after IVD, the CFT seemed to have a tendency to increase. Conclusions. Single IVD could significantly decrease macular edema and improve visual outcome for eyes with persistent long-term macular edema after macular ERM removal and the effect can be sustained as long as 6 months after the initial injection. However, in order to maintain the visual and anatomical outcome, repeat IVD might be considered if macular edema recurs. [ABSTRACT FROM AUTHOR]

Purpose: This study surveyed the novel autoantigens expressed in the orbital fat tissue of patients with Graves’ orbitopathy (GO) and explored the possibility of the autoantibodies against novel autoantigens as biomarkers for GO.Methods: We used immuno-proteomic methods to survey novel autoantigens expressed in the orbit fat tissue of GO patients and confirmed by enzyme-linked immunosorbent assay (ELISA).Results: One protein spot (aldehyde dehydrogenase 2 (ALDH2)) revealed high reactivity with the GO serum than did the healthy control serum and was further verified by ELISA. We found that the plasma anti-ALDH2 antibody level was increased in GO patients compared to healthy control donors. In addition, anti-ALDH2 antibody level was correlated with GO activity classified by clinical activity score(r = 0.588, p < 0.001, using Pearson’s correlation).Conclusions: These increased levels of anti-ALDH2 antibody in GO serum suggested that ALDH2 could attribute target autoantigen in GO, and anti-ALDH2 autoantibody might serve as a biomarker for GO and help to predict disease activity. [ABSTRACT FROM AUTHOR]

Purpose. To investigate the morphological and functional outcomes of idiopathic epiretinal membrane (ERM) surgery between three different surgical techniques: ERM peeling only, whole-piece ILM peeling, and maculorrhexis ILM peeling. Patients and Methods. This is a retrospective, consecutive, and comparative study enrolling 60 patients from Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. Surgery performed between July 2011 and June 2012 was done with ERM peeling only (group I). ERM peeling and ILM peeling as a whole piece (group II) were performed between July 2012 and July 2013. Surgery performed between August 2013 and December 2014 was done with maculorrhexis ILM peeling (group III). Main outcome measures include visual acuity change (BCVA) and central foveal thickness (CFT). Results. At 12 months postoperation, the mean BCVA in group III was significantly better than in group I and group II. Comparison of CFT reduction between the three groups revealed significantly more reduction in group III than in group II at all postoperative follow-up periods. Eyes with restoration of foveal depression were observed in 52.6% in group I, 52.4% in group III, but only 20% of eyes in group II. None of the eyes in both ILM peeling groups encountered recurrence of macular pucker formation. Conclusion. All three techniques can achieve visual acuity improvement and macular thickness reduction. Maculorrhexis ILM peeling achieves more rapid improvement of visual function, better final visual outcome, and a higher rate of normal foveal contour than whole-piece ILM peeling. [ABSTRACT FROM AUTHOR]

Background: The etiology of transient corneal haze in premature infants is not known and how it relates to clinical outcomes in premature infants is not clear. Objectives: To study associated factors of transient corneal haze in premature infants. Methods: We performed a retrospective study of 261 premature infants from retinopathy of prematurity (ROP) screening in the neonatal intensive care unit at a tertiary referral hospital. Characteristics of premature infants with and without corneal haze were analyzed by correlation tests, Chi-square tests, and logistic regressions were used for statistical analyses. Associations between corneal haze and birth weight (BW), gestational age at birth (GA), central corneal thickness, intraocular pressure, and other systemic and ophthalmic data were evaluated. Results: The incidence of corneal haze was 13.4%. Lower BW, lower GA, packed red blood cells (RBC) transfusion, more days on oxygen, older maternal age, bronchopulmonary disease, and stage 3 ROP are associated with corneal haze. The severity of corneal haze decreased with infants’ postmenstrual age. Multivariate logistic regression analyses revealed that BW and maternal age are the most important predictors of corneal haze. Conclusion: Low BW and older maternal age are the most important predictors of corneal haze in premature infants. Premature infants with corneal haze could carry more systemic and ocular morbidities. Hence they may require more clinical attention. Corneal haze is unlikely to hinder the treatment of ROP. However, it is possible that corneal haze could hinder the examination of ROP in some infants. If corneal haze does interfere with ROP screening, a closer, more conservative follow-up schedule with a senior ophthalmologist experienced in managing ROP is recommended. [ABSTRACT FROM AUTHOR]

Hypoxia-induced retinal neovascularization plays a central role in the pathogenesis of diabetic retinopathy. This study aimed to investigate whether hypoxia leads to the release of nuclear high mobility group box 1 (HMGB1) peptides from cultured retinal pigment epithelial ARPE-19 cells, to determine the effect of HMGB1 on angiogenic cytokine production and elucidate the involved signaling pathways. A chemical hypoxia mimetic agent, cobalt chloride, induced SIRT1 downregulation, HMGB1 nucleocytoplasmic relocation and extracellular release from ARPE-19 cells, implicating its autocrine function. Resveratrol treatment significantly reduced secretion of HMGB1 from ARPE-19 cells exposed to hypoxia. Cell proliferation and cell cycle analyses demonstrated that exogenous HMGB1 caused significant growth suppression and G1 cell cycle arrest in ARPE-19 cells. Morphological observations showed that HMGB1 enhanced adhesion, but suppressed migration of ARPE-19 cells. More intriguingly, HMGB1 up-regulated expression of angiofibrogenic factors in ARPE-19 cells, including VEGF, bFGF, TGF-β2, and CTGF. Signal profiling characterization indicated that HMGB1 triggered hyperphosphorylation of Akt, p38 MAPK, and NF-κB, but not that of ERK, JNK, and Smad2, whereas inhibition of PI3K, MAPK, or NF-κB significantly attenuated the HMGB1-driven cytokine overproduction in ARPE-19 cells. Functional neutralization with anti-TLR4 and -RAGE antibodies confirmed that both receptors were involved in the cytokine overproduction. In conclusion, chemically-mimicked hypoxia induced nucleocytoplasmic relocation and release of HMGB1 peptides, which in turn up-regulated the production of angiofibrogenic factors in RPE cells, thereby contributing to the pathogenesis of hypoxia-associated diabetic retinopathies. Conversely, blockades of intraocular HMGB1 bioavailability or signal activation may prevent angiofibrogenesis in development of diabetic retinopathy. [ABSTRACT FROM AUTHOR]

Background Hypoxia is the most important stimulus leading to up-regulation of vascular endothelial growth factor (VEGF) in the retina via elevation of hypoxia-inducible factors-1α (HIF-1α) protein. The purpose of this study was to test the effects of melatonin on the expression of VEGF and HIF-1α in the cultured human retinal pigment epithelial (RPE) cells under normoxia and hypoxia. Method An in vitro RPE cell hypoxia model was established by placing cells under 1% oxygen pressure or by adding cobalt chloride (CoCl2) to the culture medium. RPE cells and conditioned media were collected from cultures treated with and without melatonin under normoxia and hypoxia. The protein and RNA levels of VEGF and HIF-1α were measured by ELISA kits and RT-PCR, respectively. Result Hypoxia induced a significant increase of expression and secretion of VEGF and accumulation of HIF-1α protein in RPE cells ( P < 0.05). Melatonin at 10−5 to 10−8 M significantly inhibited hypoxia-induced expression, the secretion of VEGF and the accumulation of HIF-1α protein ( P < 0.05), but not affected expression of VEGF and HIF-1α under normoxia ( P > 0.05). Conclusion This study suggests that melatonin may have potential value in the prevention and treatment of various retinal diseases associated with increase of VEGF, vascular leakage and angiogenesis. [ABSTRACT FROM AUTHOR]

Purpose: Repeated subconjunctival injections with 5-fluorouracil (5-FU) after trabeculectomy are used in glaucoma patients for the inhibition of overproliferation in wound site. Thus, a certain amount of the drug may penetrate into epithelial layer, where it causes toxicity to corneal epithelial cells. The aim of this study was to evaluate the toxic effects of 5-FU and mechanisms of drug-induced apoptosis in cultured corneal epithelial cells.Methods: Cellular damage and the caspase pathway were estimated with a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The apoptotic characteristics were detected by flow cytometry, a TUNEL test, and western blotting in cultured corneal epithelial cells.Results: The results indicated that 5-FU was toxic to corneal epithelial cells in a time- and dose-dependent manner. Pretreatment with a general caspase inhibitor (Z-VAD-FMK), a caspase-8 inhibitor (Z-IETD-FMK), and a caspase-9 inhibitor (Z-LEHD-FMK) reversed 5-FU-induced cellular damage. Following exposure to 5-FU, a flow cytometric assay with MitoLight dye demonstrated the significant loss of mitochondrial membrane potential. A positive TUNEL test revealed that cellular DNA apoptosis occurred following exposure to 0.5, 1, and 5 mg/mL 5-FU for 15 h. Positive annexin V-FITC and negative propidium iodide (PI) staining indicated that the cell membrane exhibited apoptosis upon exposure to 1 and 5 mg/mL 5-FU for 15 h. The western blot assay demonstrated upregulation of the p21 protein but downregulation of the Bcl-2 proteins induced by 5-FU.Conclusion: These data reveal that 5-FU-induced cellular apoptosis in corneal epithelial cells may be mediated through caspase-8, caspase-9, and mitochondria-regulated pathways, as well as by upregulation of p21 and downregulation of Bcl-2-dependent signal transduction pathways. [ABSTRACT FROM AUTHOR]

Methylglyoxal (MGO), a glycolytic metabolite, induces oxidative injury and apoptotic cell death that play a pathogenetic role in age-related macular degeneration (AMD). This study examined the impact of MGO on cell proliferation and autophagy flux in retinal pigment epithelium (RPE) ARPE-19 cells and elucidated the underlying mechanism. Short-term MGO exposure suppressed cell proliferation without induction of apoptotic cell death, increased production of reactive oxygen species, and potentiated H 2 O 2 -exhibited cytotoxicity in ARPE-19 cells. Conversely, pretreatment with N-acetylcysteine, a ROS scavenger, and aminoguanidine, an MGO blocker, prevented MGO-induced growth retardation. MGO significantly enhanced autophagy flux and increased intracellular accumulation of autophagosomes, which was functionally confirmed by addition of autophagy enhancer or inhibitors. Signaling kinetic observation indicated that MGO remarkably triggered phosphorylation of Akt, ERK1/2, p38 MAPK, and JNK1/2. Blockade of kinase activity demonstrated that the hyperphosphorylation of Akt, ERK1/2, JNK, and p38 MAPK were all involved in the MGO-enhanced autophagy and growth-arresting effect in ARPE-19 cells. Moreover, pretreatment with autophagic flux inhibitors including 3-methyladenine, bafilomycin A, and chloroquine effectively ameliorated MGO- but not H 2 O 2 -mediated ARPE-19 cytotoxicity. In conclusion, modulation of autophagy flux activity by using autophagic or kinase inhibitors may be an applicable modality to treat AMD. [ABSTRACT FROM AUTHOR]

In present times, barcode decoders on mobile phones can extract the data content of QR codes. However, this convenience raises concerns about security issues when using QR codes to transmit confidential information, such as e-tickets, coupons, and other private data. Moreover, current secret hiding techniques are unsuitable for QR code applications since QR codes are module-oriented, which is different from the pixel-oriented hiding manner. In this article, we propose an algorithm to conceal confidential information by changing the modules of the QR Code. This new scheme designs the triple module groups based on the concept of the error correction capability. Additionally, this manner can conceal two secret bits by changing only one module, and the amount of hidden confidential information can be twice the original amount. As a result, the ordinary data content (such as URL) can be extracted correctly from the generated QR code by any barcode decoders, which does not affect the readability of scanning. Furthermore, only authorized users with the secret key can further extract the concealed confidential information. This designed scheme can provide secure and reliable applications for the QR system. [ABSTRACT FROM AUTHOR]

Background: Thyroid orbitopathy (TO) is a multi-system inflammatory disease characterized by orbital congestion, ocular surface disorders, restrictive myopathy, and skin lesions. The molecular and cellular processes of pathogenic formation of TO orbital fat tissues are not fully understood. In this study, a comparative proteomic analysis was conducted to investigate the importance of some differential proteins of orbital fat tissues in TO. Methods: The differential proteins were analyzed by comparing the two-dimensional gel electrophoresis (2-DE) maps of the orbital fat tissues of TO with those of normal orbital fat tissues. The 2-DE results were further verified by Western blot and immunohistochemistry. Results: Fifteen up-regulated and two down-regulated proteins in TO orbital fat tissues in comparison with the control were exhibited by 2-DE maps. The over-expressed proteins including guanine nucleotide-binding protein, isocitrate dehydrogenase (IDH), annexin A2, heat shock protein 60 (HSP 60), calreticulin (CALR), protein disulfide-isomerase A3 (PDIA3), spectrin, superoxide dismutase (SOD), and transitional endoplasmic reticulum ATPase (TER ATPase) may contribute to increased thyroid-stimulating hormone receptor (TSHR) expression and cell proliferation. The proteomic data of specific proteins are consistent with those determined by Western blot and immunohistochemistry. Conclusions: Comparison of orbital fat proteins from thyroid orbitopathy with age-matched controls shows significant differences in the proteome, and up-regulations of the specific proteins in orbital fat tissues from TO are associated with biochemical mechanisms or capacities against endoplasmic reticulum stress, mitochondria dysfunction, and cell proliferation as well as apoptosis in TO orbital fat tissues. [ABSTRACT FROM AUTHOR]

Transforming growth factor-β2 (TGF-β2) has been implicated in the pathogenesis of proliferative vitreoretinopathy (PVR) and proliferative diabetic retinopathy (PDR), due to its ability to stimulate the overproduction of pro-angiogenic factors, such as vascular endothelial growth factor (VEGF), and remodeling of the extracellular matrix (ECM). Although intravitreal triamcinolone acetonide (TA) is clinically useful in the treatment of PVR and PDR, its molecular mechanism has yet to be fully elucidated. The present study investigated whether TA treatment altered TGF-β2-driven biological effects on the behavior of cultured human retinal pigment epithelial (RPE) cells, in order to determine which signaling pathway may be essential for the pharmacological action of TA. The R-50 human RPE cell line was treated with TA in the presence of TGF-β2, followed by analyses of cell viability and contraction using cell viability and collagen gel contraction assays. VEGF mRNA expression and protein production were measured using reverse transcription-quantitative PCR and ELISA, respectively. The phosphorylation status of signaling mediators and the protein expression of type I collagen (COL1A1), α-smooth muscle actin (α-SMA), and ECM-remodeling enzymes, including MMP-2 and MMP-9, were analyzed using western blotting. The gelatinolytic activity of MMPs was detected using gelatin zymography. TA treatment exhibited no prominent cytotoxicity but markedly antagonized TGF-β2-induced cytostatic effects on RPE cell viability and TGF-β2-enhanced contractility in collagen gels. In the context of TGF-β2-related signaling, TA significantly attenuated TGF-β2-elicited Smad2, extracellular-regulated kinase (ERK)1/2 and p38 mitogen-activated protein kinase (MAPK) phosphorylation. Moreover, TA markedly mitigated TGF-β2-induced VEGF upregulation through ablation of p38 signaling activity. TA also partially attenuated TGF-β2-elicted expression of COL1A1, α-SMA, MMP-2, and MMP-9, but only suppressed TGF-β2-induced MMP-9 gelatinolytic activity. Mechanistically, the MEK/ERK signaling pathway may have a critical role in the TGF-β2-induced upregulation of COL1A1, α-SMA and MMP-9. In conclusion, TA may be considered a useful therapeutic agent for treating TGF-β2-associated intraocular angiogenesis and tissue remodeling, the underlying mechanism of which may involve the ERK and p38 MAPK signaling pathways. [ABSTRACT FROM AUTHOR]

Abstract: Pyrrolo[2,1-c][1,4]benzodiazepine (PBD) chemicals are antitumor antibiotics inhibiting nucleic acid synthesis. An indole carboxylate-PBD hybrid with six-carbon spacer structure (IN6CPBD) has been previously demonstrated to induce melanoma cell apoptosis and reduce metastasis in mouse lungs. This study aimed at investigating the efficacy of the other hybrid compound with four-carbon spacer (IN4CPBD) and elucidating its anti-metastatic mechanism. Human melanoma A375 cells with IN4CPBD treatment underwent cytotoxicity and apoptosis-associated assays. Transwell migration assay, Western blotting, and ELISA were used for mechanistic study. IN4CPBD exhibited potent melanoma cytotoxicity through interrupting G1/S cell cycle progression, increasing DNA fragmentation and hypodipoidic DNA contents, and reducing mitochondrial membrane potential. Caspase activity elevation suggested that both intrinsic and extrinsic pathways were involved in IN4CPBD-induced melanoma apoptosis. IN4CPBD up-regulated p53 and p21, thereby concomitantly derailing the equilibrium between Bcl-2 and Bax levels. Transwell migration assay demonstrated that stromal cell-derived factor-1α (SDF-1α) stimulated A375 cell motility, while kinase inhibitors treatment confirmed that Rho/ROCK, Akt, ERK1/2, and p38 MAPK pathways were involved in SDF-1α-enhanced melanoma migration. IN4CPBD not only abolished the SDF-1α-enhanced chemotactic motility but also suppressed constitutive MMP-9 and VEGF expression. Mechanistically, IN4CPBD down-regulated Akt, ERK1/2, and p38 MAPK total proteins and MYPT1 phosphorylation. In conclusion, beyond the fact that IN4CPBD induces melanoma cell apoptosis at cytotoxic dose, the interruption in the VEGF expression and the SDF-1α-related signaling at cytostatic dose may partially constitute the rationale for its in vivo anti-metastatic potency. [Copyright &y& Elsevier]

Abstract: All-trans retinoic acid (atRA) has been reported to inhibit the proliferation of retinal pigment epithelial (RPE) cells and used in treatment of proliferative vitreoretinopathy (PVR) in animal model. This study aimed at examining the effectiveness of atRA in inhibiting the extracellular matrix (ECM) biosynthesis by RPE cells and the RPE cell-mediated collagen gel contraction. Cultured RPE cells were treated with atRA and the expression of four ECM proteins (collagen types I, III, IV and laminin β1) was profiled. The results indicated that atRA treatment up-regulated de novo synthesis of collagen type I, but decreased that of laminin β1 in a dose-dependent manner. Moreover, the effect of atRA on RPE cell contraction was evaluated by measuring the area of collagen gel where RPE cells populated. Treatment with atRA significantly inhibited RPE cell-mediated collagen gel contraction. Addition of exogenous laminin nonapeptide into gels promoted RPE cell contraction, while atRA reversed the laminin-enhanced contractility. atRA treatment significantly suppressed the gene expression of integrin β3 but not αV subunit, and effectively inhibited the tyrosine phosphorylation of integrin β3 at residue 747 in RPE cells grown on laminin-coated dish, suggesting that atRA may suppress the RPE contractility through either inhibiting integrin β3 expression or abrogating the integrin β3-mediated signaling. In conclusion, atRA pharmacologically possesses a tissue-remodeling capacity and inhibits contractility of RPE cells. Therefore, atRA might be potentially a therapeutic agent for certain ocular disorders such as PVR. [Copyright &y& Elsevier]

Focuses on a study which investigated the release of vascular endothelial growth factor within the subretinal fluid in eyes with retinal detachment. Introduction to vascular endothelial growth factor; Materials and methods; Results and discussion.

This study investigated the regulatory role of microRNA 100 (miR-100) in hydrogen peroxide (H2O2)-induced apoptosis of human retinal pigment epithelial ARPE-19 cells. H2O2 induced oxidative cell death of cultured ARPE-19 cells was measured by cytotoxicity assay. qRT-PCR was used to quantify cytosolic and extracellular contents of miR-100. Kinase and miR-100 inhibition treatments were applied to determine the regulatory signaling pathways involved in cell death regulation. H2O2 dose-dependently reduced viability of ARPE-19 cells and simultaneously upregulated miR-100 levels in both cytosolic and extracellular compartments. Western blotting detection indicated that H2O2 elicited hyperphosphorylation of PI3K/Akt, ERK1/2, JNK, p38 MAPK, and p65 NF-κB. Further kinase inhibition experiments demonstrated that PI3K, p38 MAPK, and NF-κB activities were involved in oxidative-stress-induced miR-100 upregulation in ARPE-19 cells, while blockade of PI3K, JNK, and NF-κB signaling significantly attenuated the oxidative cell death. Intriguingly, MiR-100 antagomir treatment exerted a cytoprotective effect against the H2O2-induced oxidative cell death through attenuating the oxidation-induced AMPK hyperphosphorylation, restoring cellular mTOR and p62/SQSTM1 levels and upregulating heme oxygenase-1 expression. These findings support that miR-100 at least in part mediates H2O2-induced cell death of ARPE-19 cells and can be regarded as a preventive and therapeutic target for retinal degenerative disease. [ABSTRACT FROM AUTHOR]

Dyslipidemia-associated diabetic retinopathy is featured by macular edema and retinal angiogenesis. This study investigated the in vitro lipotoxicity of free fatty acids and their modulatory roles in regulation of autophagy and angiogenic factor production in cultured human retinal pigment epithelium (RPE) ARPE-19 cells. ARPE-19 cells were exposed to monounsaturated oleic acid (OA), saturated palmitic acid (PA), or both. Cell viability, cell cycle distribution, migration, and autophagy of the treated cells were monitored. Angiogenic factor production was determined by RT-qPCR and ELISA. OA, but not PA, at doses higher than 500 μM significantly induced cytostasis and lipotoxicity in ARPE-19 cells. OA exposure not only markedly enhanced autophagy flux, but also enhanced cell migration, while PA suppressed motility of RPE cells. Meanwhile, OA stimulated de novo synthesis of angiogenic factors including VEGF and bFGF in ARPE-19 cells. Mechanistically, OA treatment stimulated not only AMPK/mTOR/p70S6K signaling, but also induced hyperphosphorylation of MAPK pathway mediators, including ERK, JNK and p38 MAPK, as well as NF-κB activation. Kinase inhibition assays showed that blockade of PI3K/Akt, MAPK and NF-κB pathways prevented the OA-upregulated VEGF transcription and its peptide release. Comparatively, only NF-κB inhibition significantly suppressed bFGF peptide release from ARPE-19 cells. Out findings support the OA-exhibited cytostasis, autophagy modulation and angiogenic factor production in RPE cells. This study sheds light on the interrelationship between metabolic disorder and retinopathy and provides molecular strategies for preventing and treating choroidal neovascularization in diabetic retinopathy. • Monounsaturated oleic acid, but not saturated palmitic acid induces lipotoxicity in ARPE-19 cells • Oleic acid enhances cell migration and de novo synthesis of angiogenic factors. • Oleic acid modulates autophagy flux via AMPK/mTOR/p70S6K signaling. • Oleic acid-activated MAPK and NF-κB pathways are involved in the VEGF upregulation. • Only NF-κB activity is crucial for the inducible bFGF release from ARPE-19 cells. [ABSTRACT FROM AUTHOR]