All Title Author
Keywords Abstract


Mechanisms of Inflammation in Proliferative Vitreoretinopathy: From Bench to Bedside

DOI: 10.1155/2012/815937

Full-Text   Cite this paper   Add to My Lib

Abstract:

Proliferative vitreoretinopathy (PVR) is a vision-threatening disease and a common complication of surgery to correct rhegmatogenous retinal detachment (RRD). Several models of the pathogenesis of this disease have been described with some of these models focusing on the role of inflammatory cells and other models focusing on the role of growth factors and cytokines in the vitreous which come into contact with intraretinal and retinal pigment epithelial cells. New experiments have shed light on the pathogenesis of PVR and offer promising avenues for clinical intervention before PVR develops. One such target is the indirect pathway of activation of platelet-derived growth factor receptor alpha (PDGRα), which plays an important role in PVR. Clinical trials assessing the efficacy of 5-fluorouracil (5-FU) and low-molecular-weight heparin (LMWH), daunorubicin, and 13-cis-retinoic acid, among other therapies, have yielded mixed results. Here we review inflammatory and other mechanisms involved in the pathogenesis of PVR, we highlight important clinical trials, and we discuss how findings at the bench have the potential to be translated to the bedside. 1. Introduction Proliferative vitreoretinopathy (PVR) is a vision-threatening disease that can occur secondary to retinal detachment (RD). RD allows macrophages, retinal pigment epithelial (RPE) cells, glial cells, and fibroblasts to migrate to the vitreous, where they proliferate, survive, form extracellular matrix proteins and assemble into a membrane [1]. This membrane can attach to the retina and subsequently contract, which can cause a new retinal detachment or failure of a surgically corrected detachment [2]. PVR occurs most commonly as a complication of surgery to correct rhegmatogenous retinal detachment (RRD) and is the most common reason for the failure of this operation [3, 4]. In one study of 119 patients with RRD and no previous vitreoretinal surgery, there was a 52.9% prevalence of PVR and 26.9% prevalence of severe PVR with mean retinal detachment duration of days [5]. Visual outcomes and the anatomical success of surgery are worse for RD that is complicated by PVR and may require twice as many resources to care for as those cases of RD without PVR [6]. Here we review inflammatory and other mechanisms involved in the pathogenesis of PVR, we highlight important clinical trials, and we discuss how findings at the bench have the potential to be translated to the bedside. 2. The Macrophage Hypothesis for Development of PVR Some of the hypotheses regarding the pathogenesis of PVR have focused on the

References

[1]  D. A. Newsome, M. M. Rodrigues, and R. Machemer, “Human massive periretinal proliferation. In vitro characteristics of cellular components,” Archives of Ophthalmology, vol. 99, no. 5, pp. 873–880, 1981.
[2]  G. W. Aylward, Ophthalmology Chapter 6. 41—Proliferative Vitreoretinopathy, Mosby, 3rd edition, 2008.
[3]  S. J. Ryan, “The pathophysiology of proliferative vitreoretinopathy in its management,” American Journal of Ophthalmology, vol. 100, no. 1, pp. 188–193, 1985.
[4]  AAO, “Basic and Clinical Science Course, Section 12: Retina and Vitreous,” 2011-2012.
[5]  W. Tseng, R. T. Cortez, G. Ramirez, S. Stinnett, and G. J. Jaffe, “Prevalence and risk factors for proliferative vitreoretinopathy in eyes with rhegmatogenous retinal detachment but no previous vitreoretinal surgery,” American Journal of Ophthalmology, vol. 137, no. 6, pp. 1105–1115, 2004.
[6]  N. N. Patel, C. Bunce, R. H. Asaria, and D. G. Charteris, “Resources involved in managing retinal detachment complicated by proliferative vitreoretinopathy,” Retina, vol. 24, no. 6, pp. 883–887, 2004.
[7]  Y. N. Hui, N. Sorgente, and S. J. Ryan, “Posterior vitreous separation and retinal detachment induced by macrophages,” Graefe's Archive for Clinical and Experimental Ophthalmology, vol. 225, no. 4, pp. 279–284, 1987.
[8]  M. Weller, K. Heimann, and P. Wiedemann, “The pathogenesis of vitreoretinal proliferation and traction: a working hypothesis,” Medical Hypotheses, vol. 31, no. 2, pp. 157–159, 1990.
[9]  Y. N. Hui, R. Goodnight, N. Sorgente, and S. J. Ryan, “Fibrovascular proliferation and retinal detachment after intravitreal injection of activated macrophages in the rabbit eye,” American Journal of Ophthalmology, vol. 108, no. 2, pp. 176–184, 1989.
[10]  R. J. Davis and M. P. Czech, “Regulation of transferrin receptor expression at the cell surface by insulin-like growth factors, epidermal growth factor and platelet-derived growth factor,” The EMBO Journal, vol. 5, no. 4, pp. 653–658, 1986.
[11]  M. L. Lin, Y. P. Li, Z. R. Li, J. X. Lin, X. L. Zhou, and D. Liang, “Macrophages acquire fibroblast characteristics in a rat model of proliferative vitreoretinopathy,” Ophthalmic Research, vol. 45, no. 4, pp. 180–190, 2011.
[12]  P. Algvere and E. Kock, “Experimental fibroplasia in the rabbit vitreous. Retinal detachment induced by autologous fibroblasts,” Albrecht von Graefes Archiv fur Klinische und Experimentelle Ophthalmologie, vol. 199, no. 3, pp. 215–222, 1976.
[13]  G. Sugita, Y. Tano, and R. Machemer, “Intravitreal autotransplantation of fibroblasts,” American Journal of Ophthalmology, vol. 89, no. 1, pp. 121–130, 1980.
[14]  D. B. Chandler, F. A. Quansah, T. Hida, and R. Machemer, “A refined experimental model for proliferative vitreoretinopathy,” Graefe's Archive for Clinical and Experimental Ophthalmology, vol. 224, no. 1, pp. 86–91, 1986.
[15]  C. A. Hitchins and I. Grierson, “Intravitreal injection of fibroblasts: the pathological effects on the ocular tissues of the rabbit following an intravitreal injection of autologous skin fibroblasts,” British Journal of Ophthalmology, vol. 72, no. 7, pp. 498–510, 1988.
[16]  A. M. Abu El-Asrar, S. Struyf, J. Van Damme, and K. Geboes, “Circulating fibrocytes contribute to the myofibroblast population in proliferative vitreoretinopathy epiretinal membranes,” British Journal of Ophthalmology, vol. 92, no. 5, pp. 699–704, 2008.
[17]  P. Wiedemann, S. J. Ryan, P. Novak, and N. Sorgente, “Vitreous stimulates proliferation of fibroblasts and retinal pigment epithelial cells,” Experimental Eye Research, vol. 41, no. 5, pp. 619–628, 1985.
[18]  C. Hardwick, R. Morris, D. Witherspoon et al., “Pathologic human vitreous promotes contraction by fibroblasts: implications for proliferative vitreoretinopathy,” Archives of Ophthalmology, vol. 113, no. 12, pp. 1545–1553, 1995.
[19]  X. Z. Zheng, L. F. Du, and H. P. Wang, “A immunohistochemical analysis of a rat model of proliferative vitreoretinopathy and a comparison of the expression of TGF-β and PDGF among the induction methods,” Bosnian Journal of Basic Medical Sciences, vol. 10, no. 3, pp. 204–209, 2010.
[20]  H. Lei, M. A. Rheaume, and A. Kazlauskas, “Recent developments in our understanding of how platelet-derived growth factor (PDGF) and its receptors contribute to proliferative vitreoretinopathy,” Experimental Eye Research, vol. 90, no. 3, pp. 376–381, 2010.
[21]  A. Andrews, E. Balciunaite, F. L. Leong et al., “Platelet-derived growth factor plays a key role in proliferative vitreoretinopathy,” Investigative Ophthalmology and Visual Science, vol. 40, no. 11, pp. 2683–2689, 1999.
[22]  J. Z. Cui, A. Chiu, D. Maberley, P. Ma, A. Samad, and J. A. Matsubara, “Stage specificity of novel growth factor expression during development of proliferative vitreoretinopathy,” Eye, vol. 21, no. 2, pp. 200–208, 2007.
[23]  D. R. Hinton, S. He, M. L. Jin, E. Barron, and S. J. Ryan, “Novel growth factors involved in the pathogenesis of proliferative vitreoretinopathy,” Eye, vol. 16, no. 4, pp. 422–428, 2002.
[24]  L. J. Ricker, S. C. Dieudonné, A. G. Kessels et al., “Antiangiogenic isoforms of vascular endothelial growth factor predominate in subretinal fluid of patients with rhegmatogenous retinal detachment and proliferative vitreoretinopathy,” Retina, vol. 32, no. 1, pp. 54–59, 2012.
[25]  H. Lei, G. Velez, P. Hovland, T. Hirose, D. Gilbertson, and A. Kazlauskas, “Growth factors outside the PDGF family drive experimental PVR,” Investigative Ophthalmology and Visual Science, vol. 50, no. 7, pp. 3394–3403, 2009.
[26]  S. C. Dieudonné, E. C. La Heij, R. M. H. Diederen et al., “Balance of vascular endothelial growth factor and pigment epithelial growth factor prior to development of proliferative vitreoretinopathy,” Ophthalmic Research, vol. 39, no. 3, pp. 148–154, 2007.
[27]  S. C. Dieudonné, E. C. La Heij, R. Diederen et al., “High TGF-β2 levels during primary retinal detachment may protect against proliferative vitreoretinopathy,” Investigative Ophthalmology and Visual Science, vol. 45, no. 11, pp. 4113–4118, 2004.
[28]  G. A. Limb, B. C. Little, A. Meager et al., “Cytokines in proliferative vitreoretinopathy,” Eye (London, England), vol. 5, pp. 6–693, 1991.
[29]  S. Banerjee, V. Savant, R. A. H. Scott, S. J. Curnow, G. R. Wallace, and P. L. Murray, “Multiplex bead analysis of vitreous humor of patients with vitreoretinal disorders,” Investigative Ophthalmology and Visual Science, vol. 48, no. 5, pp. 2203–2207, 2007.
[30]  Y. Hui, Y. Shi, X. Zhang, K. Yang, and C. Yu, “TNF-alpha, IL-8 and IL-6 in the early inflammatory stage of experimental PVR model induced by macrophages,” Chinese Journal of Ophthalmology, vol. 35, no. 2, pp. 140–143, 1999.
[31]  R. H. Y. Asaria, C. H. Kon, C. Bunce et al., “Silicone oil concentrates fibrogenic growth factors in the retro-oil fluid,” British Journal of Ophthalmology, vol. 88, no. 11, pp. 1439–1442, 2004.
[32]  E. C. La Heij, M. P. H. Van de Waarenburg, H. G. T. Blaauwgeers et al., “Basic fibroblast growth factor, glutamine synthetase, and interleukin-6 in vitreous fluid from eyes with retinal detachment complicated by proliferative vitreoretinopathy,” American Journal of Ophthalmology, vol. 134, no. 3, pp. 367–375, 2002.
[33]  S. Mukherjee and C. Guidry, “The insulin-like growth factor system modulates retinal pigment epithelial cell tractional force generation,” Investigative Ophthalmology and Visual Science, vol. 48, no. 4, pp. 1892–1899, 2007.
[34]  G. I. Liou, V. A. Pakalnis, S. Matragoon et al., “HGF regulation of RPE proliferation in an IL-1β/retinal hole-induced rabbit model of PVR,” Molecular Vision, vol. 8, pp. 494–501, 2002.
[35]  S. G. Elner, V. M. Elner, G. J. Jaffe, A. Stuart, S. L. Kunkel, and R. M. Strieter, “Cytokines in proliferative diabetic retinopathy and proliferative vitreoretinopathy,” Current Eye Research, vol. 14, no. 11, pp. 1045–1053, 1995.
[36]  Y. Mitamura, S. Takeuchi, S. Yamamoto et al., “Monocyte chemotactic protein-1 levels in the vitreous of patients with proliferative vitreoretinopathy,” Japanese Journal of Ophthalmology, vol. 46, no. 2, pp. 218–221, 2002.
[37]  R. M. Strieter, S. L. Kunkel, H. J. Showell et al., “Endothelial cell gene expression of a neutrophil chemotactic factor by TNF-α, LPS, and IL-1β,” Science, vol. 243, no. 4897, pp. 1467–1469, 1989.
[38]  J. R. Bradley, “TNF-mediated inflammatory disease,” Journal of Pathology, vol. 214, no. 2, pp. 149–160, 2008.
[39]  G. A. Limb, A. Alam, O. Earley, W. Green, A. H. Chignell, and D. C. Dumonde, “Distribution of cytokine proteins within epiretinal membranes in proliferative vitreoretinopathy,” Current Eye Research, vol. 13, no. 11, pp. 791–798, 1994.
[40]  P. D. Crowe, B. N. Walter, K. M. Mohler, C. Otten-Evans, R. A. Black, and C. F. Ware, “A metalloprotease inhibitor blocks shedding of the 80-kD TNF receptor and TNF processing in T lymphocytes,” Journal of Experimental Medicine, vol. 181, no. 3, pp. 1205–1210, 1995.
[41]  D. Aderka, H. Engelmann, Y. Shemer-Avni et al., “Variation in serum levels of the soluble TNF receptors among healthy individuals,” Lymphokine and Cytokine Research, vol. 11, no. 3, pp. 157–159, 1992.
[42]  K. J. Van Zee, T. Kohno, E. Fischer, C. S. Rock, L. L. Moldawer, and S. F. Lowry, “Tumor necrosis factor soluble receptors circulate during experimental and clinical inflammation and can protect against excessive tumor necrosis factor α in vitro and in vivo,” Proceedings of the National Academy of Sciences of the United States of America, vol. 89, no. 11, pp. 4845–4849, 1992.
[43]  T. Spoettl, M. Hausmann, F. Klebl et al., “Serum soluble TNF receptor I and II levels correlate with disease activity in IBD patients,” Inflammatory Bowel Diseases, vol. 13, no. 6, pp. 727–732, 2007.
[44]  G. A. Limb, R. D. Hollifield, L. Webster, D. G. Charteris, and A. H. Chignell, “Soluble TNF receptors in vitreoretinal proliferative disease,” Investigative Ophthalmology and Visual Science, vol. 42, no. 7, pp. 1586–1591, 2001.
[45]  R. Gerli, D. Monti, O. Bistoni et al., “Chemokines, sTNF-Rs and sCD30 serum levels in healthy aged people and centenarians,” Mechanisms of Ageing and Development, vol. 121, no. 1–3, pp. 37–46, 2001.
[46]  J. Rojas, I. Fernandez, J. C. Pastor et al., “A strong genetic association between the tumor necrosis factor locus and proliferative vitreoretinopathy: the Retina 4 Project,” Ophthalmology, vol. 117, no. 12, pp. 2417–e2, 2010.
[47]  H. S. Mudhar, R. A. Pollock, C. Wang, C. D. Stiles, and W. D. Richardson, “PDGF and its receptors in the developing rodent retina and optic nerve,” Development, vol. 118, no. 2, pp. 539–552, 1993.
[48]  M. Fruttiger, A. R. Calver, W. H. Krüger et al., “PDGF mediates a neuron-astrocyte interaction in the developing retina,” Neuron, vol. 17, no. 6, pp. 1117–1131, 1996.
[49]  S. G. Robbins, R. N. Mixon, D. J. Wilson et al., “Platelet-derived growth factor ligands and receptors immunolocalized in proliferative retinal diseases,” Investigative Ophthalmology & Visual Science, vol. 35, no. 10, pp. 3649–3663, 1994.
[50]  Y. Ikuno and A. Kazlauskas, “An in vivo gene therapy approach for experimental proliferative vitreoretinopathy using the truncated platelet-derived growth factor α receptor,” Investigative Ophthalmology and Visual Science, vol. 43, no. 7, pp. 2406–2411, 2002.
[51]  J. Cui, H. Lei, A. Samad et al., “PDGF receptors are activated in human epiretinal membranes,” Experimental Eye Research, vol. 88, no. 3, pp. 438–444, 2009.
[52]  H. Lei, P. Hovland, G. Velez et al., “A potential role for PDGF-C in experimental and clinical proliferative vitreoretinopathy,” Investigative Ophthalmology and Visual Science, vol. 48, no. 5, pp. 2335–2342, 2007.
[53]  H. Lei, G. Velez, P. Hovland, T. Hirose, and A. Kazlauskas, “Plasmin is the major protease responsible for processing PDGF-C in the vitreous of patients with proliferative vitreoretinopathy,” Investigative Ophthalmology and Visual Science, vol. 49, no. 1, pp. 42–48, 2008.
[54]  R. N. Agrawal, S. He, C. Spee, J. Z. Cui, S. J. Ryan, and D. R. Hinton, “In vivo models of proliferative vitreoretinopathy,” Nature Protocols, vol. 2, no. 1, pp. 67–77, 2007.
[55]  Y. Ikuno, F. L. Leong, and A. Kazlauskas, “Attenuation of experimental proliferative vitreoretinopathy by inhibiting the platelet-derived growth factor receptor,” Investigative Ophthalmology and Visual Science, vol. 41, no. 10, pp. 3107–3116, 2000.
[56]  Y. Zheng, Y. Ikuno, M. Ohj et al., “Platelet-derived growth factor receptor kinase inhibitor AG1295 and inhibition of experimental proliferative vitreoretinopathy,” Japanese Journal of Ophthalmology, vol. 47, no. 2, pp. 158–165, 2003.
[57]  X. Li, A. Pontén, K. Aase et al., “PDGF-C is a new protease-activated ligand for the PDGF α-receptor,” Nature Cell Biology, vol. 2, no. 5, pp. 302–307, 2000.
[58]  H. Lei and A. Kazlauskas, “Growth factors outside of the platelet-derived growth factor (PDGF) family employ reactive oxygen species/Src family kinases to activate PDGF receptor α and thereby promote proliferation and survival of cells,” The Journal of Biological Chemistry, vol. 284, no. 10, pp. 6329–6336, 2009.
[59]  S. Pennock and A. Kazlauskas, “Vascular endothelial growth factor A competitively inhibits platelet-derived growth factor (PDGF)-dependent activation of PDGF receptor and subsequent signaling events and cellular responses,” Molecular and Cellular Biology, vol. 32, no. 10, pp. 1955–1966, 2012.
[60]  H. Lei, G. Velez, and A. Kazlauskas, “Pathological signaling via platelet-derived growth factor receptor α involves chronic activation of Akt and suppression of p53,” Molecular and Cellular Biology, vol. 31, no. 9, pp. 1788–1799, 2011.
[61]  H. Akiyama, S. Kachi, R. Lima E Silva et al., “Intraocular injection of an aptamer that binds PDGF-B: a potential treatment for proliferative retinopathies,” Journal of Cellular Physiology, vol. 207, no. 2, pp. 407–412, 2006.
[62]  H. Lei, G. Velez, J. Cui et al., “N-acetylcysteine suppresses retinal detachment in an experimental model of proliferative vitreoretinopathy,” American Journal of Pathology, vol. 177, no. 1, pp. 132–140, 2010.
[63]  S. Pennock, M. A. Rheaume, S. Mukai, and A. Kazlauskas, “A novel strategy to develop therapeutic approaches to prevent proliferative vitreoretinopathy,” The American Journal of Pathology, vol. 179, no. 6, pp. 2931–2940, 2011.
[64]  M. Blumenkranz, E. Hernandez, A. Ophir, and E. W. D. Norton, “5-fluorouracil: new applications in complicated retinal detachment for an established antimetabolite,” Ophthalmology, vol. 91, no. 2, pp. 122–130, 1984.
[65]  M. S. Blumenkranz, M. K. Hartzer, and D. Iverson, “An overview of potential applications of heparin in vitreoretinal surgery,” Retina, vol. 12, no. 3, pp. S71–S74, 1992.
[66]  M. S. Blumenkranz, A. Ophir, A. J. Claflin, and A. Hajek, “Fluorouracil for the treatment of massive periretinal proliferation,” American Journal of Ophthalmology, vol. 94, no. 4, pp. 458–467, 1982.
[67]  T. Ward, M. Hartzer, M. Blumenkranz, and L. R. Lin, “A comparison of 5-Fluorouridine and 5-Fluorouracil in an experimental model for the treatment of vitreoretinal scarring,” Current Eye Research, vol. 12, no. 5, pp. 397–401, 1993.
[68]  R. H. Y. Asaria, C. H. Kon, C. Bunce et al., “Adjuvant 5-fluorouracil and heparin prevents proliferative vitreoretinopathy: results from a randomized, double-blind, controlled clinical trial,” Ophthalmology, vol. 108, no. 7, pp. 1179–1183, 2001.
[69]  D. G. Charteris, G. W. Aylward, D. Wong, C. Groenewald, R. H. Y. Asaria, and C. Bunce, “A randomized controlled trial of combined 5-fluorouracil and low-molecular-weight heparin in management of established proliferative vitreoretinopathy,” Ophthalmology, vol. 111, no. 12, pp. 2240–2245, 2004.
[70]  L. Wickham, C. Bunce, D. Wong, D. McGurn, and D. G. Charteris, “Randomized controlled trial of combined 5-fluorouracil and low-molecular-weight heparin in the management of unselected rhegmatogenous retinal detachments undergoing primary vitrectomy,” Ophthalmology, vol. 114, no. 4, pp. 698–704, 2007.
[71]  V. Sundaram, A. Barsam, and G. Virgili, “Intravitreal low molecular weight heparin and 5-Fluorouracil for the prevention of proliferative vitreoretinopathy following retinal reattachment surgery,” Cochrane Database of Systematic Reviews (Online), vol. 7, article CD006421, 2010.
[72]  C. Verdoorn, V. W. Renardel de Lavalette, and J. Dalma-Weizhausz, “Cellular migration, proliferation, and contraction. An in vitro approach to a clinical problem—proliferative vitreoretinopathy,” Archives of Ophthalmology, vol. 104, no. 8, pp. 1216–1219, 1986.
[73]  P. Wiedemann, N. Sorgente, and C. Bekhor, “Daunomycin in the treatment of experimental proliferative vitreoretinopathy. Effective doses in vitro and in vivo,” Investigative Ophthalmology and Visual Science, vol. 26, no. 5, pp. 719–725, 1985.
[74]  P. Wiedemann, K. Lemmen, R. Schmiedl, and K. Heimann, “Intraocular daunorubicin for the treatment and prophylaxis of traumatic proliferative vitreoretinopathy,” American Journal of Ophthalmology, vol. 104, no. 1, pp. 10–14, 1987.
[75]  P. Wiedemann, R. D. Hilgers, P. Bauer, and K. Heimann, “Adjunctive daunorubicin in the treatment of proliferative vitreoretinopathy: results of a multicenter clinical trial,” American Journal of Ophthalmology, vol. 126, no. 4, pp. 550–559, 1998.
[76]  Y. Tano, D. Chandler, and R. Machemer, “Treatment of intraocular proliferation with intravitreal injection of triamcinolone acetonide,” American Journal of Ophthalmology, vol. 90, no. 6, pp. 810–816, 1980.
[77]  F. Koerner, A. Merz, B. Gloor, and E. Wagner, “Postoperative retinal fibrosis—a controlled clinical study of systemic steroid therapy,” Graefe's Archive for Clinical and Experimental Ophthalmology, vol. 219, no. 6, pp. 268–271, 1982.
[78]  P. A. Campochiaro, S. F. Hackett, and B. P. Conway, “Retinoic acid promotes density-dependent growth arrest in human retinal pigment epithelial cells,” Investigative Ophthalmology and Visual Science, vol. 32, no. 1, pp. 65–72, 1991.
[79]  W. C. Wu, D. N. Hu, S. Mehta, and Y. C. Chang, “Effects of retinoic acid on retinal pigment epithelium from excised membranes from proliferative vitreoretinopathy,” Journal of Ocular Pharmacology and Therapeutics, vol. 21, no. 1, pp. 44–54, 2005.
[80]  Y. C. Chang, D. N. Hu, and W. C. Wu, “Effect of oral 13-cis-retinoic acid treatment on postoperative clinical outcome of eyes with proliferative vitreoretinopathy,” American Journal of Ophthalmology, vol. 146, no. 3, pp. 440–e1, 2008.
[81]  P. C. Wu, M. H. Tai, D. N. Hu et al., “Cyclin-dependent kinase inhibitor roscovitine induces cell cycle arrest and apoptosis in rabbit retinal pigment epithelial cells,” Journal of Ocular Pharmacology and Therapeutics, vol. 24, no. 1, pp. 25–33, 2008.
[82]  I. A. Falkenstein, L. Cheng, F. Wong-Staal et al., “Toxicity and intraocular properties of a novel long-acting anti-proliferative and anti-angiogenic compound IMS2186,” Current Eye Research, vol. 33, no. 7, pp. 599–609, 2008.

Full-Text

comments powered by Disqus

Contact Us

service@oalib.com

QQ:3279437679

微信:OALib Journal