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Ma, Jie

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Ma

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Jie

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Ma, Jie

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2013 - 20156

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Author's Publications: search.filters.isAuthorOfPublication.4b78db1c-629a-44c9-bb42-c302aa07990c

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Now showing 1 - 6 of 6
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    Influence of subretinal fluid in advanced stage retinopathy of prematurity on proangiogenic response and cell proliferation
    (Molecular Vision, 2014) Ma, Jie; Mehta, Manisha; Lam, Godfrey; Cyr, Desireé; Ng, Tat Fong; Hirose, Tatsuo; Tawansy, Khaled A.; Taylor, Andrew W.; Lashkari, Kameran
    Purpose The clinical phenotype of advanced stage retinopathy of prematurity (ROP, stages 4 and 5) cannot be replicated in an animal model. To dissect the molecular events that can lead up to advanced ROP, we examined subretinal fluid (SRF) and surgically dissected retrolental membranes from patients with advanced ROP to evaluate its influences on cell proliferation, angiogenic properties, and macrophage polarity. Methods: We compared our findings to SRF collected from patients with uncomplicated rhegmatogenous retinal detachment (RD) without proliferative vitreoretinopathy and surgically dissected epiretinal membrane from eyes with macular pucker. All subretinal fluid samples were equalized for protein. The angiogenic potential of SRF from ROP eyes was measured using a combination of capillary cord formation in a fibrin clot assay, and its proliferative effect was tested with a DNA synthesis of human retinal microvascular endothelial cells. Findings were compared with SRF collected from participants with uncomplicated rhegmatogenous RD without proliferative vitreoretinopathy. The ability of SRF to induce nitric oxide production was measured in vitro using murine J774A.1 macrophages. Cytokine profiles of SRF from ROP and RD eyes were measured using a multienzyme-linked immunosorbent assay (ELISA). Fluorescent immunohistochemistry of retrolental membranes from ROP was performed to detect the presence of leukocytes and the composition of tissue macrophages using markers for M1 and M2 differentiation. Results: The cytokine composition in SRF revealed that in ROP, not only were several proangiogenic factors were preferentially elevated but also the profile of proinflammatory factors was also increased compared to the RD eyes. SRF from ROP eyes supported cell proliferation and endothelial cord formation while SRF from RD eyes had inhibitory effects. SRF from eyes with ROP but not RD robustly induced nitric oxide production in macrophages. Furthermore, fluorescent immunostaining revealed a preponderance of M1 over M2 macrophages in retrolental fibrous membranes from ROP eyes. The cytokine profile and biologic properties of SRF in ROP promote a proangiogenic environment, which supports the maintenance and proliferation of fibrous membranes associated with advanced stages of ROP. In contrast, SRF from RD eyes exhibits a suppressive environment for endothelial cell proliferation and angiogenesis. Conclusions: Our investigation demonstrates that the microenvironment in advanced ROP eyes is proangiogenic and proinflammatory. These findings suggest that management of advanced ROP should not be limited to the surgical removal of the fibrovascular membranes and antiangiogenic therapy but also directed to anti-inflammatory therapy and to promote M2 activation over M1 activity.
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    Correlation of Cytokine Levels and Microglial Cell Infiltration during Retinal Degeneration in RCS Rats
    (Public Library of Science, 2013) Liu, Yong; Yang, Xuesen; Utheim, Tor Paaaske; Guo, Chenying; Xiao, Mingchun; Liu, Yan; Yin, Zhengqin; Ma, Jie
    Microglial cells, which are immunocompetent cells, are involved in all diseases of the central nervous system. During their activation in various diseases, a variety of soluble factors are released. In the present study, the correlation between cytokine levels and microglial cell migration in the course of retinal degeneration of Royal College of Surgeons (RCS) rats was evaluated. MFG-E8 and CD11b were used to confirm the microglial cells. In the retina of RCS rats, the mRNA expression of seven genes (MFG-E8 and its integrins αυ and ß5, CD11b and the cytokines TNF-α, IL-1ß, and MCP-1) formed almost similar bimodal peak distributions, which were centred at P7 and P45 to P60. In contrast, in rdy rats, which comprised the control group, a unimodal peak distribution centred at P14 was observed. The gene expression accompanied the activation and migration of microglial cells from the inner to the outer layer of the retina during the process of degeneration. Principal component analysis and discriminant function analysis revealed that the expression of these seven genes, especially TNF-α and CD11b, positively correlated with retinal degeneration and microglial activity during retinal degeneration in RCS rats, but not in the control rats. Furthermore, linear regression analysis demonstrated a significant correlation between the expression of these genes and the activation of microglial cells in the dystrophic retina. Our findings suggest that the suppression of microglial cells and the blockade of their cytotoxic effects may constitute a novel therapeutic strategy for treating photoreceptor death in various retinal disorders.
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    Transplantation of Human Neural Progenitor Cells Expressing IGF-1 Enhances Retinal Ganglion Cell Survival
    (Public Library of Science, 2015) Ma, Jie; Guo, Chenying; Guo, Caiwei; Sun, Yu; Liao, Tiffany; Beattie, Ursula; López, Francisco J.; Chen, Dong; Lashkari, Kameran
    We have previously characterized human neuronal progenitor cells (hNP) that can adopt a retinal ganglion cell (RGC)-like morphology within the RGC and nerve fiber layers of the retina. In an effort to determine whether hNPs could be used a candidate cells for targeted delivery of neurotrophic factors (NTFs), we evaluated whether hNPs transfected with an vector that expresses IGF-1 in the form of a fusion protein with tdTomato (TD), would increase RGC survival in vitro and confer neuroprotective effects in a mouse model of glaucoma. RGCs co-cultured with hNPIGF-TD cells displayed enhanced survival, and increased neurite extension and branching as compared to hNPTD or untransfected hNP cells. Application of various IGF-1 signaling blockers or IGF-1 receptor antagonists abrogated these effects. In vivo, using a model of glaucoma we showed that IOP elevation led to reductions in retinal RGC count. In this model, evaluation of retinal flatmounts and optic nerve cross sections indicated that only hNPIGF-TD cells effectively reduced RGC death and showed a trend to improve optic nerve axonal loss. RT-PCR analysis of retina lysates over time showed that the neurotrophic effects of IGF-1 were also attributed to down-regulation of inflammatory and to some extent, angiogenic pathways. This study shows that neuronal progenitor cells that hone into the RGC and nerve fiber layers may be used as vehicles for local production and delivery of a desired NTF. Transplantation of hNPIGF-TD cells improves RGC survival in vitro and protects against RGC loss in a rodent model of glaucoma. Our findings have provided experimental evidence and form the basis for applying cell-based strategies for local delivery of NTFs into the retina. Application of cell-based delivery may be extended to other disease conditions beyond glaucoma.
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    Practicability confirmation by meta-analysis of intravitreal ranibizumab compared to photodynamic therapy to treat polypoidal choroidal vasculopathy
    (Molecular Vision, 2015) Liu, Ling; Ma, Jie; Duan, Ping; Liu, Yong; Yin, Zheng Qin
    Purpose The literatures show that photodynamic therapy (PDT) and intravitreal ranibizumab (IVR) have their own specific advantages in treating polypoidal choroidal vasculopathy (PCV). Using a meta-analysis, we want to provide some suggestions for the clinical application of the two treatments to PCV patients through a comparison of the functional outcomes in a follow-up period after administration. Methods: A comprehensive literature search was performed using several databases to assemble the controlled trials of IVR and PDT. The program of RevMan version 5.0 was used to analyze the data. The effects of two treatments on PCV were evaluated by comparing weighted mean differences (WMDs) in the change of LogMar visual acuity, central retinal thickness (CRT), and the deterioration ratio for the proportions of patients with visual reductions from the baseline. Data with homogeneity among studies were analyzed using a fixed-effect meta-analysis model; otherwise, a random-effect model was applied to data with heterogeneity. Results: Five studies are included covering 260 cases in total in this study. The outcomes of IVR treatment compared to PDT appear to significantly improve vision, decrease the central retinal thickness (CRT), and reduce the invalidation rate. The LogMar visual acuity shifts from 0.6 to 0.3 in the following 24 months and the improvement rate of visual acuity ranges from 60–70% in IVR treated patients. However, the visual acuity improvement is moderate in the PDT group. These analyses indicate that IVR is an applicable treatment in PCV patients, although PDT is able to yield about a 35% visual acuity improvement in a short-term follow-up. Our 3-D mesh modal also confirms that IVR is able to yield better effects to treat PCV than PDT. Conclusions: The analysis in this study suggests that IVR has a significant effect on the improvement of visual acuity when treating patients with PCV. Our findings clearly document that IVR can be used as a more effective therapy for long-term administration in PCV.
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    Nestin depletion induces melanoma matrix metalloproteinases and invasion
    (2015) Lee, Chung-Wei; Zhan, Qian; Lezcano, Cecilia; Frank, Markus; Huang, John; Larson, Allison; Lin, Jennifer; Wan, Marilyn T.; Lin, Ping-I; Ma, Jie; Kleffel, Sonja; Schatton, Tobias; Lian, Christine; Murphy, George
    Matrix metalloproteinases (MMPs) are key biological mediators of processes as diverse as wound healing, embryogenesis, and cancer progression. Although MMPs may be induced through multiple signaling pathways, the precise mechanisms for their regulation in cancer are incompletely understood. Because cytoskeletal changes are known to accompany MMP expression, we sought to examine the potential role of the poorly understood cytoskeletal protein, nestin, in modulating melanoma MMPs. Nestin knockdown (KD) upregulated expression of specific MMPs and MMP-dependent invasion both through extracellular matrix barriers in vitro and in peritumoral connective tissue of xenografts in vivo. Development of 3-dimensionsal melanospheres that in vitro partially recapitulate non-invasive tumorigenic melanoma growth was inhibited by nestin KD, although ECM invasion by aberrant melanospheres that did form was enhanced. Mechanistically, nestin KD-dependent melanoma invasion was associated with intracellular redistribution of phosphorylated focal adhesion kinase (pFAK) and increased melanoma cell responsiveness to transforming growth factor-beta (TGF-β), both implicated in pathways of melanoma invasion. The results suggest that the heretofore poorly understood intermediate filament, nestin, may serve as a novel mediator of MMPs critical to melanoma virulence.
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    Essential Role of MFG-E8 for Phagocytic Properties of Microglial Cells
    (Public Library of Science, 2013) Liu, Yong; Yang, Xuesen; Guo, Chenying; Nie, Pan; Liu, Yan; Ma, Jie
    Milk fat globule factor-E8 (MFG-E8) has been regarded as a key factor involved in the phagocytosis of apoptotic cells. We induced a lentivirus into the microglial cells for the augmentation or abrogation of MFG-E8 expression in mouse microglial cells, and investigated phagocytosis of phosphatidylserine tagged human red blood cells (hRBCs) in co-cultures. Increased MFG-E8 levels were associated with a significant increase in phagocytic activity compared to the controls. Conversely, phagocytosis dramitically decreased due to the abrogation of MFG-E8. In addition, the expression of the inflammatory cytokines, TNF-α and IL-1β, also increased or decreased in the microglial cells with the augmentation or abrogation of MFG-E8, respectively. Our findings indicate that the enhanced expression of MFG-E8 could increase phagocytosis of apoptotic cells; conversely, the rate of phagocytosis and the expression of inflammatory cytokines decreased when MFG-E8 expression was knocked down. Our results confirm that MFG-E8 plays an important role in phagocytosis, and possibly serves as an essential signal molecule for microglial cells.