Knockdown of ChREBP ameliorates retinal microvascular endothelial cell injury and angiogenic responses in diabetic retinopathy.

PURPOSE: To examine whether and how carbohydrate response element-binding protein (ChREBP) plays a role in diabetic retinopathy. METHODS: Western blotting was used to detect ChREBP expression and location following high glucose stimulation of Human Retinal Microvascular Endothelial Cells (HRMECs). Flow cytometry, TUNEL staining, and western blotting were used to evaluate apoptosis following ChREBP siRNA silencing. Cell scratch, transwell migration, and tube formation assays were used to determine cell migration and angiogenesis. Diabetic models for wild-type (WT) and ChREBP knockout (ChKO) mice were developed. Retinas of WT and ChKO animals were cultivated in vitro with vascular endothelial growth factor + high glucose to assess neovascular development. RESULTS: ChREBP gene knockdown inhibited thioredoxin-interacting protein and NOD-like receptor family pyrin domain containing protein 3 expression in HRMECs, which was caused by high glucose stimulation, reduced apoptosis, hindered migration, and tube formation, and repressed AKT/mTOR signaling pathway activation. Compared with WT mice, ChKO mice showed suppressed high glucose-induced alterations in retinal structure, alleviated retinal vascular leakage, and reduced retinal neovascularization. CONCLUSIONS: ChREBP deficiency decreased high glucose-induced apoptosis, migration, and tube formation in HRMECs as well as structural and angiogenic responses in the mouse retina; thus, it is a potential therapeutic target for diabetic retinopathy.

Cytokine Expression and Biomechanical Characteristics after Posterior Scleral Reinforcement Using Demineralized Bone Matrix and Allogeneic Sclera.

Background: Myopia is associated with scleral weakness and thinness, leading to visual impairment. Currently, posterior scleral reinforcement (PSR) remains the primary treatment for this condition. However, clinical practice commonly faces challenges such as insufficient donor availability and inadequate strength of allogeneic sclera materials. Therefore, in this study, we evaluated the cytokine expression and biomechanical characteristics of two types of scleral reinforcement materials (demineralized bone matrix (DBM) and allogeneic sclera) to identify the optimal material for PSR. Methods: Seventy-two two-week-old New Zealand rabbits were utilized in this study. Each rabbit eye was assigned to either an experimental group or an untreated group (no surgical intervention), which were further divided into DBM, allogenic sclera, and control groups (surgery without implantation). Samples were analyzed during different postoperative periods including the inflammatory response period at week 2, angiogenesis period at week 4, collagen formation period at week 12, and connective tissue proliferation period at week 24. Refractive power and axial length of the experimental eyes were measured at 2, 4, 12,and 24 weeks postoperatively while implanted slices with attached sclera from the DBM and Sclera group experimental eyes were collected. The same area of sclera was obtained from the sham group for immunohistochemical analysis and western blot detection to analyze levels of bFGF (Basic Fibroblast Growth Factor), CTGF (Connective Tissue Growth Factor), TGF-ß (Transforming Growth Factor ß),and Collagen I along with respective elasticity modulus and ultimate strength of the implant slice taken. Results: There were no significant differences (P > .05) in axial length and refractive power between the DBM and allogenic groups before 24 weeks, while a significant difference (P < .05) was observed compared to the control group. The levels of bFGF, CTGF, and TGF-ß in the DBM and sclera groups were significantly higher than those in the control group (P < .05). After 24 weeks, histological analyses revealed a strong connection between the implants and sclera with collagen formation. The elasticity modulus and ultimate strength of both DBM and scleral groups were significantly higher than those of the control group (P < .05). Furthermore, the DBM group exhibited a higher elastic modulus and ultimate strength compared to the scleral group (P < .05). The synthesis of collagen can be effectively promoted by bFGF, CTGF, and TGF-ß, leading to increased elastic modulus and ultimate strength which helps prevent posterior scleral expansion, thereby controlling further axial growth delay complications occurrence. Conclusion: The cytokine expression profile along with biomechanical characteristics make DBM an ideal material for posterior scleral reinforcement due to its low antigenicity, excellent biocompatibility without obvious postoperative rejection reaction as well as its ability to closely associate with autologous sclera making it widely available from various sources.

A strain of Vibrio alginolyticus isolated from Azumapecten farreri and its pathogenic mechanism using CRISPR-Cas9 technology.

Scallops have become an important aquaculture species in China because they contain high-quality protein, and scallops are important health food that combines multiple effects and high economic benefits. However, scallop aquaculture is perennially threatened by various pathogenic Vibrio species, leading to great economic losses. We obtained a strain of pathogenic bacteria, identified as Vibrio alginolyticus, from the diseased Azumapecten farreri in the scallop farming area of Huangdao District in 2018, and V. alginolyticus is one of the major shellfish pathogens. We showed that V. alginolyticus was isolated and identified as a pathogen in A. farreri for the first time. In this study, we evaluated its morphology and performed a phylogenetic analysis based on 16S rRNA gene sequencing. In addition, we performed a preliminary analysis of its pathogenic mechanisms. The Hfq protein in V. alginolyticus is an important RNA-binding protein in the quorum-sensing system that not only affects the sensitivity of Vibrio to environmental stress but also regulates a variety of functions, such as cell membrane formation, motility, and virulence towards the host. However, its effect on the pathogenesis of V. alginolyticus to A. farreri is unclear. To further investigate the pathogenic mechanism of the Hfq protein in V. alginolyticus to A. farreri, we used the CRISPR-Cas9 system to target and deplete the hfq gene fragment in V. alginolyticus and obtained the mutant strain V. ΔHfq-. We found that the peripheral flagellum of the mutant strain was lost, which reduced the motility of V. alginolyticus. Therefore, the deletion of target genes by the CRISPR/Cas9 genome editing system confirmed that the Hfq protein played a key role in reducing the ability of V. alginolyticus to infect A. farreri. In conclusion, our current findings provided valuable insights into the healthy culture of scallops.

Depletion of Fractalkine ameliorates renal injury and Treg cell apoptosis via the p38MAPK pathway in lupus-prone mice.

Fractalkine (FKN) is a chemokine with several roles, including chemotaxis; adhesion; and immune damage, which also participates in cell inflammation and apoptosis and responds to the pathogenesis of autoimmune diseases. Given the involvement of regulatory T cells (Treg) cells in autoimmune diseases, this study investigated the regulatory mechanism of FKN in renal injury and Treg apoptosis via the p38 mitogen-activated protein kinase (p38MAPK) signaling pathway in lupus-prone mice. Lupus was induced in BALB/c female mice by injection of pristane, followed by isolation of CD4+CD25+ Treg cells from the spleen of lupus model mice. To deplete FKN, mice received injection of an anti-FKN antibody, and Treg cells were transfected with FKN small-interfering RNA. Lupus mice and Treg cells were treated with the p38MAPK inhibitor SB203580 and activator U-46619, respectively, and urine protein and serum urea nitrogen, creatinine, and autoantibodies were measured and renal histopathological changes analyzed. We determined levels of FKN, phosphorylated p38 (p-p38), and forkhead box P3 (FOXP3) in renal tissue and Treg cells, and analyzed apoptosis rates and levels of key apoptotic factors in Treg cells. The renal FKN and p-p38 levels increased, whereas renal FOXP3 level decreased in lupus-prone mice. Treatment with the anti-FKN antibody and the p38MAPK inhibitor ameliorated proteinuria and renal function, significantly reducing serum autoantibody, renal FKN, and p-p38 levels while increasing renal FOXP3 level in lupus-prone mice. Moreover, FKN knockdown and administration of the p38MAPK inhibitor reduced apoptosis and levels of pro-apoptotic factors, increased levels of anti-apoptotic factors, and suppressed activation of p38MAPK signaling in Treg cells derived from lupus model mice. Furthermore, treatment with the p38MAPK activator U-46619 had the opposite effect on these cells. These data indicated that depletion of FKN ameliorated renal injury and Treg cell apoptosis via inhibition of p38MAPK signaling in lupus nephritis, suggesting that targeting FKN represents a potential therapeutic strategy for treating Lupus nephritis.

Fractalkine deficiency attenuates LPS-induced acute kidney injury and podocyte apoptosis by targeting the PI3K/Akt signal pathway.

BACKGROUND: Podocyte injury is a major biomarker of primary glomerular disease, which leads to massive proteinuria and kidney failure. The increased production of the chemokine, fractalkine (FKN, CX3CL1), is a hallmark of multiple inflammatory diseases. However, the underlying mechanism of FKN in podocyte injury remains unknown. METHODS: In this study, we performed an LPS infusion model in FKN knockout (FKN-/-, FKN-KO) mice. In cultured podocytes, we used plasmids to knockdown FKN and treated the podocytes with PI3K/Akt inhibitor (LY294002). Haematoxylin and eosin (HE) staining, Western Bolt, Co-immunoprecipitation (Co-IP), Immunofluorescence staining and flow cytometric analysis were employed to establish the role of FKN in podocyte injury. RESULTS: LPS stimulation resulted in kidney damage, increased the expression of the Bcl-2 family apoptosis protein, and decreased podocyte marker protein (nephrin, podocin and WT1) abundance compared with the WT mice. LPS-induced FKN-KO mice exhibited reduced lethality and inflammatory cell infiltration, podocyte apoptosis, and PI3K/Akt signal pathway inhibition compared to WT mice. In cultured podocytes, the interaction between FKN and the PI3K/Akt signalling pathway was well confirmed. FKN knockdown reduced podocyte apoptosis by regulating the Bcl-2 family; however, this protective effect was reversed by the co-administration of a PI3K/Akt inhibitor (LY294002). CONCLUSION: Overall, these findings reveal a novel mechanistic property of FKN, PI3K/Akt signalling, and podocyte apoptosis.

Effect of 0.02% and 0.01% atropine on astigmatism: a two-year clinical trial.

BACKGROUND: To evaluate the effects of 0.02% and 0.01% atropine eye drops on ocular and corneal astigmatism over 2 years. METHODS: A prospective clinic-controlled trail. The cohort study assessed 400 myopic children and divided them into three groups: 138 and 142 children were randomized to use either 0.02% or 0.01% atropine eye drops, respectively. They wore single-vision (SV) spectacles, with one drop of atropine applied to both eyes once nightly. Control children (n = 120) only wore SV spectacles. Spherical equivalent refractive errors (SER) and corneal curvature were measured every 4 months. The SER and corneal curvature were assessed by cycloplegic autorefraction and IOLMaster. Ocular and corneal astigmatism were calculated by Thibos vector analysis and then split into its power vector components, J0 (with-the-rule astigmatism) and J45 (oblique). RESULTS: After 2 years, the ocular astigmatism increased by -0.38 ± 0.29 D, -0.47 ± 0.38 D, -0.41 ± 0.35 D in the 0.02%, 0.01% atropine groups and control group, respectively (p = 0.15). The corresponding corneal astigmatism increased by -0.20 ± 0.34 D, -0.28 ± 0.35 D and -0.26 ± 0.26 D (p = 0.18). The ocular astigmatism J0 increased by 0.19 ± 0.28 D, 0.22 ± 0.36 D, 0.18 ± 0.31 D in the 0.02% atropine, 0.01% atropine and control groups, respectively (p = 0.65). The corresponding corneal astigmatism J0 increased by -0.05 ± 0.34 D, -0.11 ± 0.37 D and -0.13 ± 0.30 D (p = 0.23). There was a small but significant increase in ocular astigmatism (including J0) (all P < 0.05), but there were no changes in the ocular astigmatism J45 and corneal astigmatism (including J0 and J45) in the three groups over time (all p > 0.05). However, there were no significant differences in the changes in ocular astigmatism (including J0) among the three groups. CONCLUSIONS: Treatment with 0.02% and 0.01% atropine had no clinically significant effect on ocular and corneal astigmatism over 2 years. TRIAL REGISTRATION: The First Affiliated Hospital of Zhengzhou University, ChiCTR-IPD-16008844 . Registered 14/07/2016.

Improved growth of bait microalgae Isochrysis and aquacultural wastewater treatment with mixotrophic culture.

This research of mixotrophic microalgae Isochrysis 3011 with glycerol was combined with the treatment of aqua-cultural wastewater, different initial concentrations, and optimized light intensities. The algae growth rate, removal efficiencies of total nitrogen (TN) and total phosphorus (TP) were determined. Results showed that the suitable initial concentration was 0.4 g L-1, and the optimum light intensity was 60 µmol m-2 s-1. The growth of the mixotrophic group was better than that of the autotrophic culture. The biomass yield of the mixotrophic group with glycerol was 0.17 g L-1 d-1, and the removal rates of TN and TP were 73.39% and 95.61%, respectively. The content of total lipid and total protein in mixotrophic group were higher than the values of the autotrophic group. This indicates that aquaculture wastewater treatment with mixotrophic bait microalgae can obtain superior micro-algal biomass, which is also a potential technology for wastewater utilization and ecological protection.

Study of the effects of rabbit scleral fibroblasts on cellular biomechanical properties and MMP-2 expression using two modes of riboflavin/ultraviolet A wave collagen cross-linking.

OBJECTIVE: The aim of this study is to evaluate the cellular biomechanical properties and MMP-2 expression changes in rabbit scleral fibroblasts using two modes of riboflavin and ultraviolet A (UVA) collagen cross-linking (CXL). METHODS: Twenty-four New Zealand white rabbits were randomly divided into two groups, A and B. The left eye was chosen for the experimental group and the right eye for the control group. In group A, the eyes were irradiated for 30 min, with a power density of 3.0 mW/cm2. In group B, the eyes were irradiated for 9 min, with a power density of 10.0 mW/cm2. One week after CXL, full-field electroretinography was performed. Sixty days after CXL, the rabbits were sacrificed, and scleral fibroblasts were extracted from the CXL-treated sclera area and corresponding parts of control sclera and cultured. Cellular biomechanical properties were evaluated using the micropipette aspiration technique, and the MMP-2 protein expression was determined by Western blot analysis. RESULTS: There was no statistical difference in the amplitude and latency of the dark adaptation 3.0 and light adaptation 3.0 between the CXL and control eyes of groups A and B (P > 0.05). Compared with the control groups, the Young's modulus of the fibroblasts and apparent viscosity of the experimental eyes in groups A and B were increased after CXL (P < 0.05), but there was no significant difference between the two groups under different irradiation modes (P > 0.05). The MMP-2 expression in scleral fibroblasts from experimental eyes was significantly higher than that in scleral fibroblasts from control eyes in groups A and B. Under the two different irradiation modes, the MMP-2 expression in the scleral fibroblasts from experimental eyes in group A was significantly higher than that in the scleral fibroblasts from experimental eyes in group B. CONCLUSION: The riboflavin-UVA scleral CXL conducted in two different modes produced no significant side effects on the retina and could strengthen the cell biomechanical properties as well as increase the MMP-2 expression of scleral fibroblasts significantly.

Novel observations in choroidal osteoma by multispectral imaging: a pilot case series.

PURPOSE: To identify novel tumor-specific features of ossification by using multispectral imaging (MSI) in patients diagnosed with choroidal osteoma. METHODS: Six eyes of 5 patients previously diagnosed with choroidal osteoma by ocular ultrasonography and orbital computerized tomography were observed with multispectral imaging (MSI). Traditional multimodal imaging, including color fundus photograph (CFP) and enhanced depth-imaging-optical coherence tomography (EDI-OCT), fundus autofluorescence (FAF), indocyanine green angiography/fundus fluorescein angiography (ICGA/FFA), was performed. Osseous features detected by MSI such as calcification and decalcification were characterized and compared with other imaging modalities. RESULTS: In all 3 eyes with calcified choroidal osteoma (100%), MSI featured by the homogeneous reflectance in 550 nm but the beehive appearance in 600-680 nm and homogenous hyper-reflectance in 780-850 nm', indicating the compact bone in the outer layers and bone trabecula in the middle layer (Sandwich sign). The pigmentary change showed high agreement between MSI and FAF. In other 3 eyes with extensive decalcification, MSI was able to differentiate the inactive portion of the osteoma from the decalcified area. The inactive portion was characterized by geographic hyper-reflective islands with higher reflectivity border (floating island sign). Decalcified portion was featured by increased definition and reflectivity from osteoma. Partial decalcification and total decalcification can be differentiated in one decalcifying eye (33.3%). MSI revealed better the presence and border of the osteoma compared with FFA, FAF and MC (100%) in all six eyes in our study. CONCLUSIONS: MSI presented characteristic osseous-related features of choroidal osteoma, providing clear evidence for differentiating osteoblastic and osteoclastic regions and noncalcifying regions. It can contribute to en-face visualization of choroidal osteomas at different stages, providing new insight into the spectrum behavior of CO.

Effects of apelin on retinal microglial cells in a rat model of oxygen-induced retinopathy of prematurity.

This study explores the effects of apelin on retinal microglial cells in rat models of oxygen-induced retinopathy of prematurity (ROP). Totally, 274 rats were selected for establishing oxygen-induced retinopathy (OIR) models, and 92 healthy rats for control group. OIR rats were assigned into OIR, 10-5 g/L apelin, 10-4 g/L apelin, and 10-3 g/L apelin groups. Immunohistochemistry was employed to determine morphology of microglial cells and cell number. CDllb, ionized calcium-binding adapter molecule 1 (IBA-1), TNF-α, and iNOS mRNA and protein expressions were identified using RT-qPCR and Western blotting, respectively. ELISA was employed to determine the levels of VEGF and glial fibrillary acidic protein (GFAP). The amoeboid microglial cells were found in the OIR and 10-3 g/L apelin groups, while bipolar microglial cells were found in the normal control, 10-5 g/L apelin and 10-4 g/L apelin groups. In the 1, 2, 3, and 4th week after apelin treatment, there were significantly decreased bipolar microglial cells, lower mRNA and protein expressions of CDllb, IBA-1, TNF-α and iNOS, and the levels of VEGF and GFAP in the 10-4 g/L apelin group than in the OIR, 10-3 g/L apelin and 10-5 g/L apelin groups. The differences between the normal control and 10-4 g/L apelin groups are not significant. Compared with the OIR group, the 10-5 g/L apelin and 10-3 g/L apelin groups presented decreased microglial cells and mRNA and protein expressions of CDllb, IBA-1, TNF-α, and iNOS. Appropriate concentration of apelin may reduce retinal microglial cells in a rat model of oxygen-induced ROP.

Effects of Curcumin on Epidermal Growth Factor in Proliferative Vitreoretinopathy.

BACKGROUND/AIMS: Proliferative vitreoretinopathy (PVR) is a common refractory eye disease that causes blindness and occurs after retinal detachment or retinal reattachment. Epidermal growth factor (EGF) has been shown to play an important role in the migration and proliferation of retinal pigment epithelium (RPE) cells, which promote PVR. Curcumin inhibits RPE cell proliferation, but it is not known whether it participates in the formation of PVR. Curcumin regulates the biological functions of EGF, which plays important roles in the development of PVR. This study aimed to evaluate the effect of curcumin on the regulation of EGF in PVR. METHODS: Rabbit RPE cells were cultured, and EGF expression was detected by immunocytochemistry. MTT assay was conducted to determine cell proliferation induced by different concentrations of EGF. Immunocytochemical staining was used to detect EGF expression after treatment with curcumin at varying concentrations. Real-time PCR (RT-PCR) and western blot analysis were used to detect the concentrations of EGF mRNA and protein after treatment with curcumin. After RPE cells and curcumin were injected into experimental rabbit eyes, the cornea, aqueous humor, lens, and vitreous opacity were observed and recorded simultaneously by indirect ophthalmoscopy, fundus color photography, and B-ultrasonography. The vitreous body was extracted, and the EGF content in the vitreous humor was measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: At each time point (24, 48, and 72 h), cell proliferation gradually increased with increasing EGF concentrations (0, 3, 6, and 9 ng/mL) in a dose-dependent manner. Cell proliferation between EGF concentrations of 9 and 12 ng/mL were no different, which suggested that 9 ng/mL EGF was the best concentration to use to stimulate RPE cell proliferation in vitro. Under all EGF concentrations (0, 3, 6, 9, and 12 ng/mL), RPE cell proliferation increased with time (from 24 to 72 h), suggesting a time-effect relationship. Curcumin downregulated EGF expression in RPE cells, which also indicated time-effect and dose-effect relationships. The best curcumin concentration for the inhibition of EGF expression was 15 µg/mL. RT-PCR and western blot analyses indicated that the EGF mRNA and expression of the protein in RPE cells treated with curcumin significantly decreased with time. Ocular examinations revealed that the vitreous opacity was lower and the proliferative membrane was thinner in the curcumin group compared with the control group. The PVR grade and the incidence of retinal detachment were significantly lower in the experimental group than in the control group. ELISA results showed that the EGF content in vitreous humor was higher in the control group than in the curcumin group. The curcumin and control groups were significantly different at each time point. CONCLUSION: Curcumin inhibited RPE cell proliferation by downregulating EGF and thus effectively inhibited the initiation and development of PVR.

Inhibitory Effects of Plumbagin on Retinal Pigment Epithelial Cell Epithelial-Mesenchymal Transition In Vitro and In Vivo.

BACKGROUND This study aimed to explore the effects of plumbagin (PLB) on epithelial-to-mesenchymal transition in retinal pigment epithelial (RPE) cells and in proliferative vitreoretinopathy (PVR) rabbit models. MATERIAL AND METHODS Rabbit RPE cells were exposed to various concentrations (0, 5, 15, and 25 µM) of PLB. Motility, migration, and invasion of PLB-treated cells were determined in vitro using Transwell chamber assays and scratch wound assays. The contractile ability was evaluated by cell contraction assay. Expression of matrix metalloproteinases (MMPs) and epithelial-mesenchymal transition (EMT) markers were assessed by western blotting. Furthermore, PLB was injected in rabbit eyes along with RPE cells after gas compression of the vitreous. The presence of PVR was determined by indirect ophthalmoscopy on days 1, 7, 14, and 21 after injection. Also, optical coherence tomography (OCT), ultrasound images, electroretinograms (ERG), and histopathology were used to assess efficacy and toxicity. RESULTS PLB significantly inhibited the migration and invasion of RPE cells. The agent also markedly reduced cell contractive ability. Furthermore, PLB treatment resulted in the decreased expression of MMP-1, MMP2, α-SMA, and the protection of ZO-1. In addition, the PLB-treated eyes showed lower PVR grades than the untreated eyes in rabbit models. PLB exhibited a wide safety margin, indicating no evidence of causing retinal toxicity. CONCLUSIONS PLB effectively inhibited the EMT of rabbit RPE cells in vitro and in the experimental PVR models. The results open new avenues for the use of PLB in prevention and treatment of PVR.

Effect of Biodegradable Scleral Plugs Containing Curcumin on Proliferative Vitreoretinopathy.

BACKGROUND: This study aimed to explore the inhibitory effect of biodegradable scleral plugs containing curcumin on rabbits with proliferative vitreoretinopathy (PVR). MATERIALS AND METHODS: The biodegradable scleral plugs containing curcumin were prepared by dissolving PLGA [poly(lactide-co-glycolide)] and curcumin. In total, 30 rabbits were divided into 2 groups: the model group received a vitreous injection of self-blood, and the treatment group received a vitreous injection of self-blood plus biodegradable scleral implants containing 1.5 mg of curcumin. On days 1, 3, 7, 14, 21, and 28 after the operation, clinical observations and PVR classifications were performed. Then, after vitreous samples were collected, different cytokines were detected using antibody chip technology. RESULTS: The scleral plug was 5 mm in length and 1 mm in diameter. Clinical observation showed marked inflammation in the model group. The development grade of PVR in the treatment group was lower than that in the model group (p < 0.05). The outcome of antibody chip technology showed that the expression levels of IL-1α, IL-1ß, IL-8, leptin, MMP-9, NCAM, and TNF-α in the treatment group at different time points were significantly lower than those in the model group (p < 0.05). CONCLUSION: Curcumin might have great potential as a therapeutic agent for PVR by inhibiting various inflammatory factors.

Plumbagin induces RPE cell cycle arrest and apoptosis via p38 MARK and PI3K/AKT/mTOR signaling pathways in PVR.

BACKGROUND: This study aimed to explore the effects of plumbagin (PLB) on ARPE-19 cells and underlying mechanism. METHODS: Cultured ARPE-19 cells were treated with various concentrations (0, 5, 15, and 25 µM) of PLB for 24 h or with 15 µM PLB for 12, 24 and 48 h. Then cell viability was evaluated by MTT assay and DAPI staining, while apoptosis and cell cycle progression of ARPE cells were assessed by flow cytometric analysis. Furthermore, the level of main regulatory proteins was examinated by Western boltting and the expression of relative mRNA was tested by Real-Time PCR. RESULTS: PLB exhibited potent inducing effects on cell cycle arrest at G2/M phase and apoptosis of ARPE cells via the modulation of Bcl-2 family regulators in a concentration- and time-dependent manner. PLB induced inhibition of phosphatidylinositol 3-kinase (PI3K) and p38 mitogen-activated protein kinase (p38 MAPK) signaling pathways contributing to the anti-proliferative activities in ARPE cells. CONCLUSIONS: This is the first report to show that PLB could inhibit the proliferation of RPE cells through down-regulation of modulatory signaling pathways. The results open new avenues for the use of PLB in prevention and treatment of proliferative vitreoretinopathy.

Excimer Laser Versus Phakic Intraocular Lenses for Myopia and Astigmatism: A Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: Meta-analysis of randomized controlled trials (RCTs) which compared excimer laser refractive surgery and phakic intraocular lenses (PIOLs) for the treatment of myopia and astigmatism. METHODS: An electronic literature search was performed using the PubMed, EBSCO, CNKI, and Cochrane Library database to identify prospective RCTs which compared excimer laser refractive surgery and PIOL with a follow-up time of at least 12 months. Efficacy, accuracy, safety outcomes, and complications were analyzed by standardized mean difference, risk ratio, and the pooled estimates according to a fixed effect model or random effect model. RESULTS: This review included 5 RCTs with a sum of 405 eyes. The range of myopia was 6.0 to 20.0 D with up to 4.0 D of astigmatism. The PIOL group was more likely to achieve a spherical equivalence within±1.0 D of target refraction at 12 months postoperatively (P=0.009), and was less likely to lose one or more lines of best spectacle corrected visual acuity than the LASER group (P=0.002). On the whole, there is no significant difference in efficacy and complications between the two kinds of surgeries. CONCLUSIONS: This meta-analysis indicated that PIOLs were safer and more accurate within 12 months of follow-up compared with excimer laser surgical for refractive errors.

Comparison of intraocular pressure andvault after implantation of implantable collamer lens with and without a central hole.

BACKGROUD: The Implantable Collamer Lens (ICL) has been used widely for refractive errors, We performed this prospective randomized comparative study to compare postoperative intraocular pressure (IOP) and vaults of the eyes implanted with conventional ICL and central hole ICL. METHODS: This study evaluated 44 eyes of 22 patients who underwent central hole ICL implantation in one eye and conventional ICL implantation in the other eye by randomization assignment. noncontact intraocular pressure were performed on 6 h, 1 day, 3 days, 1 week, 2 weeks, 1 month, 3 months and 6 months, while ICL vaults were measured on 1 day, 1 week, 1 month and 6 months. RESULTS: The IOP of both eyeswithcentral hole and conventional ICLrosetemporarily during the first month after surgeries, especially on 1 day and 2 weeks points postoperatively. The IOP ofeyes with central hole ICL was higher than that of conventionl ICL. The vaults ofeyes with central hole and conventional ICL decreased slightly with time but did not significantly affect the postoperative IOP. CONCLUSIONS: Despite the sensitivity of viscoelastic agents or inflammation, this newly developed central hole ICL implantation appears to be equivalent in safty and effcacy to conventional ICL implantation for the correction of ametropia. TRIAL REGISTRATION: Current Controlled Trials ChiCTR-INR-16008896 . Retrospectively registered 24 July 2016.

Insulin use and risk of diabetic macular edema in diabetes mellitus: a systemic review and meta-analysis of observational studies.

BACKGROUND: Diabetes mellitus is a common and serious disorder. A search of the literature reveals no comprehensive quantitative assessment of the association between insulin use and incidence of diabetic macular edema. Therefore, we performed a meta-analysis of observational studies to evaluate the effect of insulin use on the risk of developing macular edema. MATERIAL/METHODS: Comparative studies published until May 2014 were searched through a comprehensive search of the Medline, Embase, and the Cochrane Library electronic databases. A systematic review and quantitative analysis of comparative studies reporting the effect of insulin use on the incidence of macular edema was performed. All analyses were performed using the Review Manager (RevMan) v.5 (Nordic Cochrane Centre, Copenhagen, Denmark). RESULTS: A total of 202 905 individuals were included in the present meta-analysis. In a random-effects meta-analysis, the use of insulin was found to be associated with increased risk of macular edema (RR, 3.416; 95% CI, 2.417-4.829; I2, 86.6%). Analysis that just included high-quality studies showed that insulin use increased the risk of macular edema (RR, 2.728; 95% CI, 1.881-3.955; I2=77.7%). In cohort studies (RR, 4.509; 95% CI, 3.100-6.559; I2, 77.7%) but not in case-control studies (RR, 1.455; 95% CI, 0.520 to 4.066; I2, 95.9%), increased incidence of macular edema was observed. CONCLUSIONS: The results of this meta-analysis of observational studies demonstrate that insulin use is a risk factor for diabetic macular edema. However, available data are still sparse, and in-depth analyses of the assessed associations in the context of additional longitudinal studies are highly desirable to enable more precise estimates and a better understanding of the role of insulin use in incidence of diabetic macular edema.

NEDD4L Promotes IκBα Ubiquitination and Degradation in the Pathogenesis of Diabetic Retinopathy.

PURPOSE: The dysregulation of NF-κB signaling activity plays an important role in the pathogenesis of diabetic retinopathy (DR). This study explored the association between NEDD4L and IκBα in DR. METHODS: The rat model of diabetes was established and altered retinal vascular permeability in these rats was examined through an Evans blue dye assay. A range of glucose concentrations were used to treat retinal vascular endothelial cells (RVECs). The cells viability and apoptosis were assessed through MTT and flow cytometry, while shifts in cell permeability were examined by transendothelial resistance (TEER) and FITC dextran assay. The interaction of NEDD4L and IκBα was tested by Co-IP, while mRNA and protein levels were assessed via qPCR and Western blotting, respectively. RESULTS: High glucose suppressed proliferative activity of RVECs, and promoted apoptosis and the protein level of NEDD4L and NF-κB p65, but decreased IκBα. NEDD4L knockdown reversed the changes in inflammation, oxidative stress, and permeability in RVECs exposed to high glucose. Similarly, NEDD4L silencing reverted observed TEER decreases, increased monolayer permeability to FITC dextran, and ZO-1 and Claudin-5 downregulation in response to high glucose. Conversely, the impact of NEDD4L overexpression was reversed by the NF-κB inhibitor PDTC treatment. NEDD4L induced the ubiquitination of IκBα in an IKK-2-dependent manner. Moreover, siNEDD4L treatment alleviated the symptoms of DR through the inactivation of NF-κB signaling in vivo. CONCLUSIONS: NEDD4L could enhance inflammation, oxidative stress, and permeability in the retinal vascular endothelium by facilitating the ubiquitination of IκBα in an IKK-2-dependent manner. Our results support a role for NEDD4L in the pathogenesis of DR.