Xiaorong Li

Tianjin Eye Hospital, T’ien-ching-shih, Tianjin Shi, China

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Publications (28)69.41 Total impact

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    ABSTRACT: Corneal chemical burns are common ophthalmic injuries that may result in permanent visual impairment. Although significant advances have been achieved on the treatment of such cases, the structural and functional restoration of a chemical burn-injured cornea remains challenging. The applications of polysaccharide hydrogel and subconjunctival injection of mesenchymal stem cells (MSCs) have been reported to promote the healing of corneal wounds. In this study, polysaccharide was extracted from Hardy Orchid and mesenchymal stem cells (MSCs) were derived from Sprague-Dawley rats. Supplementation of the polysaccharide significantly enhanced the migration rate of primarily cultured rat corneal epithelial cells. We examined the therapeutic effects of polysaccharide in conjunction with MSCs application on the healing of corneal alkali burns in rats. Compared with either treatment alone, the combination strategy resulted in significantly better recovery of corneal epithelium and reduction in inflammation, neovascularization and opacity of healed cornea. Polysaccharide and MSCs acted additively to increase the expression of anti-inflammatory cytokine (TGF-β), antiangiogenic cytokine (TSP-1) and decrease those promoting inflammation (TNF-α), chemotaxis (MIP-1α and MCP-1) and angiogenesis (VEGF and MMP-2). This study provided evidence that Hardy Orchid derived polysaccharide and MSCs are safe and effective treatments for corneal alkali burns and that their benefits are additive when used in combination. We concluded that combination therapy with polysaccharide and MSCs is a promising clinical treatment for corneal alkali burns and may be applicable for other types of corneal disorder.
    PLoS ONE 03/2015; 10(3):e0119725. DOI:10.1371/journal.pone.0119725 · 3.53 Impact Factor
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    ABSTRACT: The objective of the study was to evaluate the amended International Classification of Headache Disorders (third edition, beta version, ICHD-3 beta) with a retrospective analysis. A total of 22 patients diagnosed with painful ophthalmoplegia and Tolosa-Hunt syndrome (THS) in our hospital were retrospectively studied. The following clinical data were collected: symptoms, signs, location of inflammatory tissue, time interval of paresis following the onset of pain, pain and signs of resolution, follow-up and relapse. Pain and diplopia were found in 22 (100 %) and 20 cases (91 %). The sympathetic nerve was involved in 6 cases (27 %). Paresis followed the pain for an average of 8 ± 5.87 days. Serial magnetic resonance imaging (MRI) revealed granulomatous lesion that was visible in 20 patients (91 %). 19 patients (86 %) demonstrated the lesions located in the cavernous sinus, orbital apex or superior orbital fissure. One lesion extended to the intracranial structure. Pain was relieved in 20 cases (91 %) within 72 h and no patient had complete relief from paresis. According to our study, we think the time course of relief should be undefined. Headache location is hard to describe accurately. Normal MRI should be involved in THS diagnoses. The lesion of THS can extend beyond the cavernous sinus and the orbit. The time interval between headache and paresis can exceed 2 weeks.
    Neurological Sciences 03/2015; 36(6). DOI:10.1007/s10072-015-2124-2 · 1.50 Impact Factor
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    ABSTRACT: Pathological retinal neovascularization, including retinopathy of prematurity and age-related macular degeneration, is the most common cause of blindness worldwide. Insulin-like growth factor-1 (IGF-1) has a direct mitogenic effect on endothelial cells, which is the basis of angiogenesis. Vascular endothelial growth factor (VEGF) activation in response to IGF-1 is well documented; however, the molecular mechanisms responsible for the termination of IGF-1 signaling are still not completely elucidated. Here, we show that the polypyrimidine tract-binding protein-associated splicing factor (PSF) is a potential negative regulator of VEGF expression induced by IGF stimulation. Functional analysis demonstrated that ectopic expression of PSF inhibits IGF-1-stimulated transcriptional activation and mRNA expression of the VEGF gene, whereas knockdown of PSF increased IGF-1-stimulated responses. PSF recruited Hakai to the VEGF transcription complex, resulting in inhibition of IGF-1-mediated transcription. Transfection with Hakai siRNA reversed the PSF-mediated transcriptional repression of VEGF gene transcription. In summary, these results show that PSF can repress the transcriptional activation of VEGF stimulated by IGF-1 via recruitment of the Hakai complex and delineate a novel regulatory mechanism of IGF-1/VEGF signaling that may have implications in the pathogenesis of neovascularization in ocular diseases.
    Cell and Tissue Research 02/2015; 360(2). DOI:10.1007/s00441-014-2104-5 · 3.33 Impact Factor
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    ABSTRACT: Autophagy, a highly conserved self-degradation process that occurs under both physiological and pathological conditions, provides the raw material and energy for cell regeneration under normal circumstances. Dysregulated autophagy under diseased conditions may cause protein accumulation, organelle dysfunction, and even cell death. Recent studies have shown that autophagy regulates the structural integrity and physiological functions of retinal photoreceptor cells and contributes to the pathogenesis of retinopathies such as retinal detachment, age-related macular degeneration, retinitis pigmentosa, and Leber's congenital amaurosis. In this review, we discuss the role of autophagy in photoreceptor cell survival and death in retinal physiology and diseases, and suggest the possibility that autophagy-targeting therapy may be a new strategy for retinal diseases marked by photoreceptor cell death.
    Critical Reviews in Eukaryotic Gene Expression 01/2015; 25(1). DOI:10.1615/CritRevEukaryotGeneExpr.2015012376 · 2.39 Impact Factor
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    Zhenna Chen, Yan Shao, Xiaorong Li
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    ABSTRACT: Proliferative vitreoretinopathy (PVR) is the major cause of failure in patients undergoing surgery for rhegmatogenous retinal detachment (RRD). Characterized by the formation of an abnormal contractile membrane within the eye, PVR can cause tractional retinal redetachment. Epithelial-to-mesenchymal transition (EMT), in which epithelial cells morphologically and phenotypically transdifferentiate into mesenchymal cells, is the major pathological process implicated in PVR. Among the various cell types involved in the process, retinal pigment epithelium cells are primary contributors although, after decades of research, the mechanisms underlying EMT have remained elusive. Recently, signaling pathways, some involving growth factors, have been demonstrated to contribute to EMT. In this article, we review research to date about the roles of such signaling, including including transforming growth factor-beta-, hepatocyte growth factor-, platelet-derived growth factor-, and Notch-, Wnt/β-catenin-, and Hippo-signaling pathways, in the EMT of PVR.
    Molecular vision 01/2015; 21:706-10. · 2.25 Impact Factor
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    ABSTRACT: Purpose:To test the long-term effects of different regimens of mesenchymal stem cell (MSC) administration in a recurrent experimental autoimmune uveitis (rEAU) model in rats, and compare the efficacy of MSC with dexamethasone (DXM). Methods:One or two courses of MSC treatments were applied to R16-specific T cell induced rEAU rats before or after disease onsets. DXM injections were given for 7 days or 50 days continuously after disease onsets. Clinical appearances were observed until the 50th day post transfer. On the 10th day, T cells from control and MSC groups were analyzed by flow cytometry. Supernatants from the proliferation assay and aqueous humor were collected for cytokine detection. Functions of T cells and APCs in spleens were also studied by lymphocyte proliferation assays. Results:One course of MSC therapy, administered after disease onset, led to a lasting therapeutic effect, with a decreased incidence, reduced mean clinical score, and reduced retinal impairment after 50 days of observation, while multiple courses of treatment did not improve the therapeutic benefit. Although DXM and MSCs equally reduced the severity of the first episode of rEAU, the effect of DXM was shorter lasting, and DXM therapy failed to control the disease even with long periods of treatment. MSCs significantly decreased T helper 1 (Th1) and Th17 responses, suppressed the function of antigen-presenting cells, and upregulated T regulatory cells. Conclusions:These results suggested that MSCs might be new corticosteroid spring agents, while providing fewer side effects and longer lasting suppressive effects for recurrent uveitis.
    Investigative Ophthalmology &amp Visual Science 08/2014; 55(9). DOI:10.1167/iovs.14-14788 · 3.66 Impact Factor
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    ABSTRACT: Functional analysis of single TLRs in vivo is necessary to understand how they shape the ocular inflammation involved in uveitis. In this study we explored the role and mechanisms of TLR2 agonists on the autoreactive Th17 response in Experimental autoimmune uveitis (EAU). Treatment by peptidoglycan (PGN), a specific TLR2 agonist, remarkably increased mRNA levels of Th17-lineage genes IL-17A, IL-21 and RORγt and promoted Ag-specific Th17 response in EAU mice. A mixture of PGN and IRBP161-180 could effectively induce EAU in the absence of CFA. PGN treatment also enhanced the pathogenic activities of activated Ag-specific Th17 cells in vivo. PGN significantly increased the production of IL-1β, IL-6 and IL-23 of DCs and enhanced their ability to promote IL-17(+) uveitogenic T cell. Enhanced immunostimulatory activities of PGN-DCs depend on p38 activation. Inhibition of p38 MAPK activity dramatically decreased IL-17 gene expression and Ag-specific Th17 responses stimulated by PGN-DCs. Our findings suggest that PGN treatment dramatically promotes the IL-17(+) uveitogenic T cell responses via enhancing the immunostimulatory activities of DCs. This effect may be mediated, at least in part, by the activation of p38 signaling pathway in DCs.
    Clinical & Experimental Immunology 06/2014; · 3.28 Impact Factor
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    ABSTRACT: Stem cell therapy has shown encouraging results for neurodegenerative diseases. The retina provides a convenient locus to investigate stem cell functions and distribution in the nervous system. In the current study, we investigated the therapeutic potential of bone marrow mesenchymal stem cells (MSCs) by systemic transplantation in a laser-induced retinal injury model. MSCs from C57BL/6 mice labeled with green fluorescent protein (GFP) were injected via the tail vein into mice after laser photocoagulation. We found that the average diameters of laser spots and retinal cell apoptosis were decreased in the MSC-treated group. Interestingly, GFP-MSCs did not migrate to the injured retina. Further examination revealed that the mRNA expression levels of glial fibrillary acidic protein and matrix metalloproteinase-2 were lower in the injured eyes after MSC transplantation. Our results suggest that intravenously injected MSCs have the ability to inhibit retinal cell apoptosis, reduce the inflammatory response and limit the spreading of damage in the laser-injured retina of mice. Systemic MSC therapy might play a role in neuroprotection, mainly by regulation of the intraocular microenvironment.
    International Journal of Molecular Sciences 06/2014; 15(6):9372-85. DOI:10.3390/ijms15069372 · 2.34 Impact Factor
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    ABSTRACT: To observe the change of semaphorin 3A (SEMA3A) expression in the retina of oxygen induced retinopathy (OIR) in rats and to investigate its influence on retinal degeneration in OIR.
    [Zhonghua yan ke za zhi] Chinese journal of ophthalmology 06/2014; 50(6):440-7.
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    ABSTRACT: Oxidative stress and apoptosis are among the earliest lesions of diabetic retinopathy. This study sought to examine the anti-oxidative and anti-apoptotic effects of α-melanocyte-stimulating hormone (α-MSH) in early diabetic retinas and to explore the underlying mechanisms in retinal vascular endothelial cells. Sprague-Dawley rats were injected intravenously with streptozocin to induce diabetes. The diabetic rats were injected intravitreally with α-MSH or saline. At week 5 after diabetes, the retinas were analyzed for reactive oxygen species (ROS) and gene expression. One week later, the retinas were processed for terminal deoxynucleotidyl transferase dUTP nick-end labeling staining and transmission electron microscopy. Retinal vascular endothelial cells were stimulated by high glucose (HG) with or without α-MSH. The expression of Forkhead box O genes (Foxos) was examined through real-time PCR. The Foxo4 gene was overexpressed in endothelial cells by transient transfection prior to α-MSH or HG treatment, and oxidative stress and apoptosis were analyzed through CM-H2DCFDA and annexin-V assays, respectively. In diabetic retinas, the levels of H2O2 and ROS and the total anti-oxidant capacity were normalized, the apoptotic cell number was reduced, and the ultrastructural injuries were ameliorated by α-MSH. Treatment with α-MSH also corrected the aberrant changes in eNOS, iNOS, ICAM-1, and TNF-α expression levels in diabetic retinas. Furthermore, α-MSH inhibited Foxo4 up-regulation in diabetic retinas and in endothelial cells exposed to HG, whereas Foxo4 overexpression abrogated the anti-oxidative and anti-apoptotic effects of α-MSH in HG-stimulated retinal vascular endothelial cells. α-MSH normalized oxidative stress, reduced apoptosis and ultrastructural injuries, and corrected gene expression levels in early diabetic retinas. The protective effects of α-MSH in retinal vascular endothelial cells may be mediated through the inhibition of Foxo4 up-regulation induced by HG. This study suggests an α-MSH-mediated potential intervention approach to early diabetic retinopathy and a novel regulatory mechanism involving Foxo4.
    PLoS ONE 04/2014; 9(4):e93433. DOI:10.1371/journal.pone.0093433 · 3.53 Impact Factor
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    Bo Yu, Xiaomin Zhang, Xiaorong Li
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    ABSTRACT: The functional mechanisms of mesenchymal stem cells (MSCs) have become a research focus in recent years. Accumulating evidence supports the notion that MSCs act in a paracrine manner. Therefore, the biological factors in conditioned medium, including exosomes and soluble factors, derived from MSC cultures are being explored extensively. The results from most investigations show that MSC-conditioned medium or its components mediate some biological functions of MSCs. Several studies have reported that MSC-derived exosomes have functions similar to those of MSCs, such as repairing tissue damage, suppressing inflammatory responses, and modulating the immune system. However, the mechanisms are still not fully understood and the results remain controversial. Compared with cells, exosomes are more stable and reservable, have no risk of aneuploidy, a lower possibility of immune rejection following in vivo allogeneic administration, and may provide an alternative therapy for various diseases. In this review, we summarize the properties and biological functions of MSC-derived exosomes and discuss the related mechanisms.
    International Journal of Molecular Sciences 03/2014; 15(3):4142-4157. DOI:10.3390/ijms15034142 · 2.34 Impact Factor
  • Fang Tian, Hong Zhang, Xiaorong Li
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    ABSTRACT: Femtosecond assisted phacoemulsification is being used in clinic widely. There have been many reports about its safety and effectiveness. In our country, femtophaco is launching and being developed gradually. The early clinical results and experiences showed that femtosecond lasers assisted cataract surgery had less complications and good repeatability with a much shorter learning curve. More importantly, it provided a standardized and precise platform and would become a milestone in the technology renovation of cataract surgery.
    [Zhonghua yan ke za zhi] Chinese journal of ophthalmology 02/2014; 50(2):133-136.
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    ABSTRACT: Background To evaluate color Doppler imaging (CDI) as the primary imaging modality in the diagnosis of pediatric orbital capillary hemangioma. Methods This is a retrospective study of 36 consecutive cases of orbital capillary hemangiomas between January 2006 and July 2011. Data on demographic details, clinical findings, gray-scale ultrasonography, CDI characteristics, treatment, and follow-up period were reviewed. Results The mean age of onset was 7 weeks. Twenty-nine (81%) lesions presented as eyelid masses, whereas seven (19%) presented as exophthalmos. Nineteen (53%) tumors were located on the upper eyelid, seven (19%) on the lower eyelid, six (17%) in the medial canthus, and one on both upper and lower eyelids. Ultrasonography depicted a heterogeneous, well-defined, irregular tumor with a low or moderate echogenicity. All lesions presented with abundant color blood flow on CDI. The intralesional blood flow had a mean peak systolic velocity of 37.5 ± 24.5 cm/second, and a mean resistance index of 0.69 ± 0.16, representing a shift in the pulse Doppler toward high velocity and high resistance. After a single intratumoral injection of betamethasone, 18 cases (50%) resolved. Additionally, 15 (42%) and four (11%) cases resolved after two injections and three injections, respectively. Only three (8%) masses persisted after three injections within the follow-up period. Conclusion The blood flow characteristics of CDI play a vital role in the differentiation of orbital capillary hemangiomas from other orbital lesions. The availability and lack of adverse effects of CDI enable its utilization in the early clinical diagnosis of pediatric orbital capillary hemangioma.
    Journal of the Chinese Medical Association 01/2014; DOI:10.1016/j.jcma.2014.02.009 · 0.89 Impact Factor
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    ABSTRACT: Tissue-engineering approach can result in significant bone regeneration. We aimed to reconstruct the segmental orbital rim defects with antigen-free bovine cancellous bone (BCB) scaffolds combined with bone marrow mesenchymal stem cells (BMSCs) in rats. BCB was prepared by degreasing, deproteinization and partly decalcification. BMSCs isolated from green fluorescent protein (GFP) transgenic rats were osteogenically induced and seeded onto BCB scaffolds to construct induced BMSCs/BCB composites. An 8-mm full-thickness defect on the rat inferior-orbit rim was established. Induced BMSCs/BCB composites cultured for 5 days were implanted into the orbital defects as the experimental group. Noninduced BMSCs/BCB group, BCB group and exclusive group were set. General condition, spiral CT, 3D orbital reconstruction, histological and histomorphometric analysis were performed after implantation. BCB presented reticular porous structure. GFP-BMSCs adhering to BCB appeared bright green fluorescence and grew vigorously. Infection and graft dislocation were not observed. In induced BMSCs/BCB group, CT and 3D reconstruction showed perfect orbital repair situation. Histological analysis indicated BCB was mostly biodegraded; newly formed bone and complete synostosis were observed. The percentage of newly formed bone was (57.12 +/- 6.28) %. In contrast, more residual BCB, less newly formed bone and nonunion were observed in the noninduced BMSCs/BCB group. Slowly absorbed BCB enwrapped by fibrous connective tissue and a small amount of new bone occurred in BCB group. Fibrous connective tissue appeared in exclusive group. Antigen-free bovine cancellous bone that retains natural bone porous structure and moderate mechanical strength with elimination of antigen is the ideal carrier for mesenchymal stem cells in vitro. BCB combined with BMSCs is a promising composite for tissue engineering, and can effectively reconstruct the orbit rim defects in rats.
    Albrecht von Graæes Archiv für Ophthalmologie 03/2013; 251(5). DOI:10.1007/s00417-013-2300-0 · 2.33 Impact Factor
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    ABSTRACT: Mesenchymal stem cells (MSCs) are being extensively explored as a promising treatment for autoimmune diseases. We recently reported that MSCs could ameliorate experimental autoimmune uveoretinitis (EAU) in rats. In this study, we further examined the effects of MSCs on the dynamics of T cell subsets in both eye and spleen and their cytokine production during the course of EAU. We focused on when and where the MSCs had inhibitory effects on Th1 and Th17 cells and how long the inhibitory effect lasted, so as to provide more mechanistic evidence for MSCs on the treatment of uveitis. Compared to the control group, administration of MSCs significantly decreased the production of Th1 and Th17 cytokines, while elevated the production of Th2 and Treg cytokines (IL-10 and TGF-b) during the entire course of EAU. Correspondingly, the dynamic levels of IL-17 in the aqueous humor (AqH) were reduced in MSCs treated rats, Moreover, the ratio of Th17/Treg cells in both spleen and eye was decreased. These results provide powerful evidence that MSCs can negatively regulate both Th1 and Th17 responses and restore the balance of Th17/Tregs in the whole course of EAU, which is important for the regression of the disease.
    Clinical & Experimental Immunology 01/2013; DOI:10.1111/cei.12080 · 3.28 Impact Factor
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    ABSTRACT: Therapeutic modalities targeting vascular endothelial growth factor (VEGF) have been used to treat neovascularization and macular edema. However, anti-VEGF treatment alone may cause up-regulation of connective tissue growth factor (CTGF) in the retina, increasing the risk of fibrosis and tractional retinal detachment. Therefore, in this study, we employ a novel dual-target intervention that involves intravitreal injection of the VEGF inhibitor ranibizumab and a transfection reagent-treated non-viral vector carrying anti-CTGF short hairpin RNA (shRNA) driven by human RNA polymerase III promoter U6. The effects of the dual-target intervention on the expression of VEGF and CTGF and on microvessel ultrastructure were examined in retina of streptozocin-induced diabetic rats. CTGF was significantly up-regulated at week 8 after diabetic induction, whereas VEGF was not up-regulated until week 10. The high expression of both genes was maintained at week 12. Transmission electron microscopy also revealed progressive exacerbation of microvessel ultrastructure during the same period. In addition, ranibizumab significantly lowered VEGF but elevated CTGF mRNA, whereas CTGF shRNA significantly reduced the mRNA levels of both CTGF and VEGF in diabetic retinas. Importantly, dual-target intervention normalized the transcript levels of both target genes and ameliorated retinal microvessel ultrastructural damage better than either single-target intervention. These results suggest the advantages of dual-target over single-target interventions in diabetic retina and reveal a novel therapeutic modality for diabetic retinopathy.
    International Journal of Molecular Sciences 01/2013; 15(1):1606-24. DOI:10.3390/ijms15011606 · 2.34 Impact Factor
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    ABSTRACT: Introduction of antigen into anterior chamber (AC) induces a deviant immune response termed anterior chamber-associated immune deviation (ACAID) that protects the eye from inflammatory destruction consequent to a systemic immune response. Mesenchymal stem cells (MSCs) are capable of modulating a wide range of immune responses. However, the effects of systemic administration of MSCs on ACAID have not been explored. In this study, C57BL/6 mice were inoculated with ovalbumin in the AC to induce ACAID, control group received AC injection of solvent alone. Immediately after the AC injection, the mice were injected through the tail vein with human Umbilical Cord-derived MSCs (hUC-MSC) or phosphate buffer saline. All animals were subcutaneously immunized with ovalbumin one week later. Delayed-type hypersensitivity assay was performed another week following immunization. The splenic monocytes were then isolated, cultured and stimulated with ovalbumin. Levels of IL-10, TGF-β, and IFN-γ in the culture media were measured by ELISA. The frequency of CD4(+) T cells positive for CD25 and Foxp3 and CD8(+) T cells positive for Foxp3 were determined by flow cytometry. The results showed that the AC inoculation of ovalbumin induced significantly less ear swelling than controls, confirming that ACAID was established. MSCs potentiated IL-10 and TGF-β production, further suppressed IFN-γ secretion from the splenic monocytes in ACAID mice, and enhanced expansion of CD4(+)CD25(+)Foxp3(+) and CD8(+)Foxp3(+) regulatory T cells isolated from the spleen of ACAID mice. Therefore, our study, for the first time, provides clear evidence that systemic administration of MSCs augments production of cytokines and expansion of Tregs from ACAID spleens, which may contribute to promotion and maintenance of ACAID.
    International immunopharmacology 11/2012; 15(1). DOI:10.1016/j.intimp.2012.11.007 · 2.71 Impact Factor
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    ABSTRACT: Mesenchymal stem cells (MSCs) are promising candidates for immunomodulatory therapy that are currently being tested in several organ transplant rejection models. In this study, we tested the immunomodulatory effects of MSC injection in a rat model of corneal allograft rejection. MSCs were isolated and cultured from bone marrow of Wistar rats. A rat corneal allograft rejection model was established using Wistar rats as donors and Lewis rats as recipients. Lewis rats were randomly separated into 12 groups and treated with MSCs alone or MSCs combined with Cyclosporin A (CsA) at different doses. In MSC-treated rats, the T cell response to ConA was evaluated, Th1/Th2 cytokines produced by T lymphocytes were measured, and the number of CD4+CD25+Foxp3+ regulatory T cells (Treg) was assessed. Results demonstrated that postoperative injection of MSCs prolonged graft survival time. MSCs significantly inhibited proliferation of pathogenic T cells in vitro and prevented T cell response in vivo (p < 0.05). Postoperative injection also reduced Th1 pro-inflammatory cytokines and elevated IL-4 cytokine secretion from T lymphocytes derived from cornea-transplanted rats. In addition, Tregs were upregulated by MSC treatment. Unexpectedly, the application of MSCs combined with low dose CsA therapy (1 mg/kg) accelerated graft rejection compared with postoperative MSC therapy alone. However, when 2 mg/kg CsA was given together with MSCs, graft survival was significantly prolonged. These results suggested that MSCs could exert therapeutic effect against corneal allograft rejection, and further investigation of combined MSC and CsA treatment be required as opposite effects were observed depending on CsA dose.
    Experimental Eye Research 07/2012; 102:44-9. DOI:10.1016/j.exer.2012.06.008 · 3.02 Impact Factor
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    ABSTRACT: The authors studied the therapeutic effect of rat mesenchymal stem cells (MSCs) on experimental autoimmune uveoretinitis (EAU) induced in rats by peptide 1169-1191 of the interphotoreceptor retinoid-binding protein (IRBP). The authors intravenously injected syngeneic (isolated from Lewis rats) or allogeneic (isolated from Wistar rats) MSCs into IRBP-induced EAU Lewis rats, either before disease onset (simultaneous with immunization, preventive protocol) or at different time points after disease onset (therapeutic protocol). T-cell response to IRBP 1169-1191 from MSC-treated rats was evaluated, Th1/Th2/Th17 cytokines produced by lymphocytes were measured, and CD4(+)CD25(+) regulatory T cells (Treg) were detected. MSC administration before disease onset not only strikingly reduced the severity of EAU, it also delayed the onset of the disease. MSC administration was also effective after disease onset and at the peak of disease, but not after disease stabilization. Clinical efficacy for all treatments was consistent with reduced cellular infiltrates and milder uveal and retinal impairment. T-cell response to IRBP 1169-1191 from MSC-treated rats was inhibited. MSCs significantly decreased the production of IFN-γ and IL-17 and increased the production of IL-10 of T lymphocytes from EAU rats either in vivo or in vitro. Allogeneic and syngeneic MSCs showed a similar immunosuppression potential with regard to clinical effect, T cell proliferation, and cytokine secretion, and MSC therapy upregulated Treg cells. These data suggest that the immunoregulatory properties of MSCs effectively interfere with the autoimmune attack in the course of EAU through the comprehensive modulation of systemic autoimmunity.
    Investigative ophthalmology & visual science 02/2011; 52(6):3143-52. DOI:10.1167/iovs.10-6334 · 3.66 Impact Factor
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    ABSTRACT: To investigate the earliest histological changes of the retina after laser treatment of diabetic retinopathy by using Spectral domain optical coherence tomography (SD-OCT, Heidelberg Engineering, Heidelberg, Germany). This study examined 320 laser burns from 16 eyes of 12 patients with early severe non-proliferative diabetic retinopathy (NPDR) that underwent laser photocoagulation according to the protocol which the Early Treatment Diabetic Retinopathy Study (ETDRS) recommended. SD-OCT scan was performed before the laser treatment, then 1 hour, 24 hours, 48 hours, 72 hours and 1 week after treatment. The main outcome measure was thickness change in outer retina (OR) in the region localized to the laser treatment. The alterations of retinal thickness at the location of the laser burns mainly occurred within the retinal layers that expand from the outer plexiform layer (OPL) to the outer highly reflective layer (HRL) (IS/OS). From 1 hour to 48 hours after laser treatment, the thickness of retina, from OPL to the HRL, increased with time. At 48 hours post- treatment, the increase of retinal thickness from OPL to the HRL reached a peak. At 72 hours, the thickness of retina from the OPL to the HRL began to decrease as a result of the outward migration of OPL towards the retinal pigment epithelial (RPE). At 1 week post- treatment, hyporeflectivity at the level of IS/OS and RPE atrophy was observed in the areas corresponding with the laser burns; the thickness of retina from the OPL to the HRL was essentially within normal thickness. This study demonstrates the subtle in vivo imaging changes of laser lesion and the trend of earliest changes in the thickness of the retina in the level of OPL-HRL, first increasing then subsequently decreasing as shown by SD-OCT in DR post laser treatment.
    Albrecht von Graæes Archiv für Ophthalmologie 12/2010; 248(12):1705-11. DOI:10.1007/s00417-010-1348-3 · 2.33 Impact Factor