Skip to main content
SpringerLink
Log in

Utility of Induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelium for an In Vitro Model of Proliferative Vitreoretinopathy

  • Chapter
  • First Online:
Pluripotent Stem Cells in Eye Disease Therapy

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1186))

Abstract

The advent of stem cell technology, including the technology to induce pluripotency in somatic cells, and direct differentiation of stem cells into specific somatic cell types, has created an exciting new field of scientific research. Much of the work with pluripotent stem (PS) cells has been focused on the exploration and exploitation of their potential as cells/tissue replacement therapies for personalized medicine. However, PS and stem cell-derived somatic cells are also proving to be valuable tools to study disease pathology and tissue-specific responses to injury. High-throughput drug screening assays using tissue-specific injury models have the potential to identify specific and effective treatments that will promote wound healing. Retinal pigment epithelium (RPE) derived from induced pluripotent stem cells (iPS-RPE) are well characterized cells that exhibit the phenotype and functions of in vivo RPE. In addition to their role as a source of cells to replace damaged or diseased RPE, iPS-RPE provide a robust platform for in vitro drug screening to identify novel therapeutics to promote healing and repair of ocular tissues after injury. Proliferative vitreoretinopathy (PVR) is an abnormal wound healing process that occurs after retinal tears or detachments. In this chapter, the role of iPS-RPE in the development of an in vitro model of PVR is described. Comprehensive analyses of the iPS-RPE response to injury suggests that these cells provide a physiologically relevant tool to investigate the cellular mechanisms of the three phases of PVR pathology: migration, proliferation, and contraction. This in vitro model will provide valuable information regarding cellular wound healing responses specific to RPE and enable the identification of effective therapeutics.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Smith AG (2001) Embryo-derived stem cells: of mice and men. Annu Rev Cell Dev Biol 17:435–462

    Article  CAS  PubMed  Google Scholar 

  2. Weissman IL, Anderson DJ, Gage F (2001) Stem and progenitor cells: origins, phenotypes, lineage commitments, and transdifferentiations. Annu Rev Cell Dev Biol 17:387–403

    Article  CAS  PubMed  Google Scholar 

  3. Gurdon JB, Melton DA (2008) Nuclear reprogramming in cells. Science 322:1811–1815

    Article  CAS  PubMed  Google Scholar 

  4. Liao SY, Tse HF (2013) Multipotent (adult) and pluripotent stem cells for heart regeneration: what are the pros and cons? Stem Cell Res Ther 4:151

    Article  PubMed  PubMed Central  Google Scholar 

  5. Evans MJ, Kaufman MH (1981) Establishment in culture of pluripotential cells from mouse embryos. Nature 292:154–156

    Article  CAS  PubMed  Google Scholar 

  6. Martin GR (1981) Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc Natl Acad Sci U S A 78:7634–7638

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Lancaster MA, Knoblich JA (2014) Organogenesis in a dish: modeling development and disease using organoid technologies. Science 345:1247125

    Article  CAS  PubMed  Google Scholar 

  8. Ko HC, Gelb BD (2014) Concise review: drug discovery in the age of the induced pluripotent stem cell. Stem Cells Transl Med 3:500–509

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Park IH, Arora N, Huo H, Maherali N, Ahfeldt T, Shimamura A, Lensch MW, Cowan C, Hochedlinger K, Daley GQ (2008) Disease-specific induced pluripotent stem cells. Cell 134:877–886

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Onder TT, Daley GQ (2012) New lessons learned from disease modeling with induced pluripotent stem cells. Curr Opin Genet Dev 22:500–508

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Jang J, Yoo JE, Lee JA, Lee DR, Kim JY, Huh YJ, Kim DS, Park CY, Hwang DY, Kim HS, Kang HC, Kim DW (2012) Disease-specific induced pluripotent stem cells: a platform for human disease modeling and drug discovery. Exp Mol Med 44:202–213

    Article  CAS  PubMed  Google Scholar 

  12. Okita K, Ichisaka T, Yamanaka S (2007) Generation of germline-competent induced pluripotent stem cells. Nature 448:313–317

    Article  CAS  PubMed  Google Scholar 

  13. Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663–676

    Article  CAS  PubMed  Google Scholar 

  14. Hyun I (2010) The bioethics of stem cell research and therapy. J Clin Invest 120:71–75

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Kaini RR, Shen-Gunther J, Cleland JM, Greene WA, Wang HC (2016) Recombinant xeno-free vitronectin supports self-renewal and pluripotency in protein-induced pluripotent stem cells. Tissue Eng Part C Methods 22:85. https://doi.org/10.1089/ten.TEC.2015.0180

    Article  CAS  PubMed  Google Scholar 

  16. Condic ML, Rao M (2010) Alternative sources of pluripotent stem cells: ethical and scientific issues revisited. Stem Cells Dev 19:1121–1129

    Article  PubMed  PubMed Central  Google Scholar 

  17. Cramer AO, MacLaren RE (2013) Translating induced pluripotent stem cells from bench to bedside: application to retinal diseases. Curr Gene Ther 13:139–151

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Kim K, Zhao R, Doi A, Ng K, Unternaehrer J, Cahan P, Huo H, Loh YH, Aryee MJ, Lensch MW, Li H, Collins JJ, Feinberg AP, Daley GQ (2011) Donor cell type can influence the epigenome and differentiation potential of human induced pluripotent stem cells. Nat Biotechnol 29:1117–1119

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Oliveira PH, da Silva CL, Cabral JM (2014) Concise review: genomic instability in human stem cells: current status and future challenges. Stem Cells 32:2824–2832

    Article  CAS  PubMed  Google Scholar 

  20. Peterson SE, Loring JF (2014) Genomic instability in pluripotent stem cells: implications for clinical applications. J Biol Chem 289:4578–4584

    Article  CAS  PubMed  Google Scholar 

  21. Toivonen S, Ojala M, Hyysalo A, Ilmarinen T, Rajala K, Pekkanen-Mattila M, Aanismaa R, Lundin K, Palgi J, Weltner J, Trokovic R, Silvennoinen O, Skottman H, Narkilahti S, Aalto-Setala K, Otonkoski T (2013) Comparative analysis of targeted differentiation of human induced pluripotent stem cells (hiPSCs) and human embryonic stem cells reveals variability associated with incomplete transgene silencing in retrovirally derived hiPSC lines. Stem Cells Transl Med 2:83–93

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, Nie J, Jonsdottir GA, Ruotti V, Stewart R, Slukvin II, Thomson JA (2007) Induced pluripotent stem cell lines derived from human somatic cells. Science 318:1917–1920

    Article  CAS  PubMed  Google Scholar 

  23. Woltjen K, Michael IP, Mohseni P, Desai R, Mileikovsky M, Hamalainen R, Cowling R, Wang W, Liu P, Gertsenstein M, Kaji K, Sung HK, Nagy A (2009) piggyBac transposition reprograms fibroblasts to induced pluripotent stem cells. Nature 458:766–770

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Ye L, Chang JC, Lin C, Qi Z, Yu J, Kan YW (2010) Generation of induced pluripotent stem cells using site-specific integration with phage integrase. Proc Natl Acad Sci U S A 107:19467–19472

    Article  PubMed  PubMed Central  Google Scholar 

  25. Yu J, Hu K, Smuga-Otto K, Tian S, Stewart R, Slukvin II, Thomson JA (2009) Human induced pluripotent stem cells free of vector and transgene sequences. Science 324:797–801

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Zhou W, Freed CR (2009) Adenoviral gene delivery can reprogram human fibroblasts to induced pluripotent stem cells. Stem Cells 27:2667–2674

    Article  CAS  PubMed  Google Scholar 

  27. Fusaki N, Ban H, Nishiyama A, Saeki K, Hasegawa M (2009) Efficient induction of transgene-free human pluripotent stem cells using a vector based on Sendai virus, an RNA virus that does not integrate into the host genome. Proc Jpn Acad Ser B Phys Biol Sci 85:348–362

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Narsinh KH, Jia F, Robbins RC, Kay MA, Longaker MT, Wu JC (2011) Generation of adult human induced pluripotent stem cells using nonviral minicircle DNA vectors. Nat Protoc 6:78–88

    Article  CAS  PubMed  Google Scholar 

  29. Warren L, Manos PD, Ahfeldt T, Loh YH, Li H, Lau F, Ebina W, Mandal PK, Smith ZD, Meissner A, Daley GQ, Brack AS, Collins JJ, Cowan C, Schlaeger TM, Rossi DJ (2010) Highly efficient reprogramming to pluripotency and directed differentiation of human cells with synthetic modified mRNA. Cell Stem Cell 7:618–630

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Kim D, Kim CH, Moon JI, Chung YG, Chang MY, Han BS, Ko S, Yang E, Cha KY, Lanza R, Kim KS (2009) Generation of human induced pluripotent stem cells by direct delivery of reprogramming proteins. Cell Stem Cell 4:472–476

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Brouwer M, Zhou H, Nadif KN (2016) Choices for induction of pluripotency: recent developments in human induced pluripotent stem cell reprogramming strategies. Stem Cell Rev 12:54–72

    Article  CAS  Google Scholar 

  32. Schlaeger TM, Daheron L, Brickler TR, Entwisle S, Chan K, Cianci A, DeVine A, Ettenger A, Fitzgerald K, Godfrey M, Gupta D, McPherson J, Malwadkar P, Gupta M, Bell B, Doi A, Jung N, Li X, Lynes MS, Brookes E, Cherry AB, Demirbas D, Tsankov AM, Zon LI, Rubin LL, Feinberg AP, Meissner A, Cowan CA, Daley GQ (2015) A comparison of non-integrating reprogramming methods. Nat Biotechnol 33:58–63

    Article  CAS  PubMed  Google Scholar 

  33. Buchholz DE, Hikita ST, Rowland TJ, Friedrich AM, Hinman CR, Johnson LV, Clegg DO (2009) Derivation of functional retinal pigmented epithelium from induced pluripotent stem cells. Stem Cells 27:2427–2434

    Article  CAS  PubMed  Google Scholar 

  34. Carr AJ, Vugler AA, Hikita ST, Lawrence JM, Gias C, Chen LL, Buchholz DE, Ahmado A, Semo M, Smart MJ, Hasan S, da Cruz L, Johnson LV, Clegg DO, Coffey PJ (2009) Protective effects of human iPS-derived retinal pigment epithelium cell transplantation in the retinal dystrophic rat. PLoS One 4:e8152

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Muniz A, Ramesh KR, Greene WA, Choi JH, Wang HC (2015) Deriving retinal pigment epithelium (RPE) from induced pluripotent stem (iPS) cells by different sizes of embryoid bodies. J Vis Exp. https://doi.org/10.3791/52262

  36. Kokkinaki M, Sahibzada N, Golestaneh N (2011) Human induced pluripotent stem-derived retinal pigment epithelium (RPE) cells exhibit ion transport, membrane potential, polarized vascular endothelial growth factor secretion, and gene expression pattern similar to native RPE. Stem Cells 29:825–835

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Muniz A, Greene WA, Plamper ML, Choi JH, Johnson AJ, Tsin AT, Wang HC (2014) Retinoid uptake, processing, and secretion in human iPS-RPE support the visual cycle. Invest Ophthalmol Vis Sci 55:198–209

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Wang HC, Greene WA, Kaini RR, Shen-Gunther J, Chen HI, Cai H, Wang Y (2014) Profiling the microRNA expression in human iPS and iPS-derived retinal pigment epithelium. Cancer Inform 13:25–35

    PubMed  PubMed Central  Google Scholar 

  39. Greene WA, Muniz A, Plamper ML, Kaini RR, Wang HC (2014) MicroRNA expression profiles of human iPS cells, retinal pigment epithelium derived from iPS, and fetal retinal pigment epithelium. J Vis Exp. https://doi.org/10.3791/51589:e51589

  40. Li Y, Tsai YT, Hsu CW, Erol D, Yang J, Wu WH, Davis RJ, Egli D, Tsang SH (2012) Long-term safety and efficacy of human-induced pluripotent stem cell (iPS) grafts in a preclinical model of retinitis pigmentosa. Mol Med 18:1312–1319

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Schwartz SD, Regillo CD, Lam BL, Eliott D, Rosenfeld PJ, Gregori NZ, Hubschman JP, Davis JL, Heilwell G, Spirn M, Maguire J, Gay R, Bateman J, Ostrick RM, Morris D, Vincent M, Anglade E, Del Priore LV, Lanza R (2015) Human embryonic stem cell-derived retinal pigment epithelium in patients with age-related macular degeneration and Stargardt’s macular dystrophy: follow-up of two open-label phase 1/2 studies. Lancet 385:509–516

    Article  PubMed  Google Scholar 

  42. Song WK, Park KM, Kim HJ, Lee JH, Choi J, Chong SY, Shim SH, Del Priore LV, Lanza R (2015) Treatment of macular degeneration using embryonic stem cell-derived retinal pigment epithelium: preliminary results in Asian patients. Stem Cell Rep 4:860–872

    Article  CAS  Google Scholar 

  43. Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131:861–872

    Article  CAS  PubMed  Google Scholar 

  44. Wang NK, Tosi J, Kasanuki JM, Chou CL, Kong J, Parmalee N, Wert KJ, Allikmets R, Lai CC, Chien CL, Nagasaki T, Lin CS, Tsang SH (2010) Transplantation of reprogrammed embryonic stem cells improves visual function in a mouse model for retinitis pigmentosa. Transplantation 89:911–919

    Article  PubMed  PubMed Central  Google Scholar 

  45. Nguyen HV, Li Y, Tsang SH (2015) Patient-specific iPSC-derived RPE for modeling of retinal diseases. J Clin Med 4:567–578

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Singh R, Shen W, Kuai D, Martin JM, Guo X, Smith MA, Perez ET, Phillips MJ, Simonett JM, Wallace KA, Verhoeven AD, Capowski EE, Zhang X, Yin Y, Halbach PJ, Fishman GA, Wright LS, Pattnaik BR, Gamm DM (2013) iPS cell modeling of best disease: insights into the pathophysiology of an inherited macular degeneration. Hum Mol Genet 22:593–607

    Article  CAS  PubMed  Google Scholar 

  47. Yang J, Li Y, Chan L, Tsai YT, Wu WH, Nguyen HV, Hsu CW, Li X, Brown LM, Egli D, Sparrow JR, Tsang SH (2014) Validation of genome-wide association study (GWAS)-identified disease risk alleles with patient-specific stem cell lines. Hum Mol Genet 23:3445–3455

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Cereso N, Pequignot MO, Robert L, Becker F, De Luca V, Nabholz N, Rigau V, De Vos J, Hamel CP, Kalatzis V (2014) Proof of concept for AAV2/5-mediated gene therapy in iPSC-derived retinal pigment epithelium of a choroideremia patient. Mol Ther Methods Clin Dev 1:14011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Polinati PP, Ilmarinen T, Trokovic R, Hyotylainen T, Otonkoski T, Suomalainen A, Skottman H, Tyni T (2015) Patient-specific induced pluripotent stem cell-derived RPE cells: understanding the pathogenesis of retinopathy in long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency. Invest Ophthalmol Vis Sci 56:3371–3382

    Article  CAS  PubMed  Google Scholar 

  50. Song MJ, Bharti K (2016) Looking into the future: using induced pluripotent stem cells to build two and three dimensional ocular tissue for cell therapy and disease modeling. Brain Res 1638:2–14

    Article  CAS  PubMed  Google Scholar 

  51. Rehan S, Javaid Z, Al-Bermani A (2015) Unilateral subretinal fibrosis and uveitis syndrome. Scott Med J 60:e4–e6

    Article  CAS  PubMed  Google Scholar 

  52. Lobler M, Buss D, Kastner C, Mostertz J, Homuth G, Ernst M, Guthoff R, Wree A, Stahnke T, Fuellen G, Voelker U, Schmitz KP (2013) Ocular fibroblast types differ in their mRNA profiles—implications for fibrosis prevention after aqueous shunt implantation. Mol Vis 19:1321–1331

    PubMed  PubMed Central  Google Scholar 

  53. Chen KJ, Sun MH, Lai CC (2012) Massive submacular fibrosis after ocular blunt injury. Arch Ophthalmol 130:1126

    Article  PubMed  Google Scholar 

  54. Bianchi E, Ripandelli G, Feher J, Plateroti AM, Plateroti R, Kovacs I, Plateroti P, Taurone S, Artico M (2015) Occlusion of retinal capillaries caused by glial cell proliferation in chronic ocular inflammation. Folia Morphol (Warsz) 74:33–41

    Article  CAS  Google Scholar 

  55. Herschler J (1977) Trabecular damage due to blunt anterior segment injury and its relationship to traumatic glaucoma. Trans Sect Ophthalmol Am Acad Ophthalmol Otolaryngol 83:239–248

    CAS  PubMed  Google Scholar 

  56. Aylward GW, Lawson J, McCarry B, Lee JP, Fells P (1992) The surgical treatment of traumatic Brown syndrome. J Pediatr Ophthalmol Strabismus 29:276–283

    CAS  PubMed  Google Scholar 

  57. Garcia GH, Goldberg RA, Shorr N (1998) The transcaruncular approach in repair of orbital fractures: a retrospective study. J Craniomaxillofac Trauma 4:7–12

    CAS  PubMed  Google Scholar 

  58. Dubois L, Steenen SA, Gooris PJ, Bos RR, Becking AG (2016) Controversies in orbital reconstruction-III. Biomaterials for orbital reconstruction: a review with clinical recommendations. Int J Oral Maxillofac Surg 45:41–50

    Article  CAS  PubMed  Google Scholar 

  59. Dubois L, Steenen SA, Gooris PJ, Mourits MP, Becking AG (2015) Controversies in orbital reconstruction—II. Timing of post-traumatic orbital reconstruction: a systematic review. Int J Oral Maxillofac Surg 44:433–440

    Article  CAS  PubMed  Google Scholar 

  60. Dubois L, Steenen SA, Gooris PJ, Mourits MP, Becking AG (2015) Controversies in orbital reconstruction—I. Defect-driven orbital reconstruction: a systematic review. Int J Oral Maxillofac Surg 44:308–315

    Article  CAS  PubMed  Google Scholar 

  61. Mendes S, Campos A, Beselga D, Campos J, Neves A (2014) Traumatic maculopathy 6 months after injury: a clinical case report. Case Rep Ophthalmol 5:78–82

    Article  PubMed  PubMed Central  Google Scholar 

  62. Campos J, Campos A, Beselga D, Mendes S, Neves A, Sousa JP (2013) Punctate inner choroidopathy: a clinical case report. Case Rep Ophthalmol 4:155–159

    Article  PubMed  PubMed Central  Google Scholar 

  63. Pastor JC (1998) Proliferative vitreoretinopathy: an overview. Surv Ophthalmol 43:3–18

    Article  CAS  PubMed  Google Scholar 

  64. Kantelip B, Bacin F (1985) Intraocular fibrosis after perforating injury of the posterior segment. Experimental study. J Fr Ophtalmol 8:245–253

    CAS  PubMed  Google Scholar 

  65. Cockerham GC, Rice TA, Hewes EH, Cockerham KP, Lemke S, Wang G, Lin RC, Glynn-Milley C, Zumhagen L (2011) Closed-eye ocular injuries in the Iraq and Afghanistan wars. N Engl J Med 364:2172–2173

    Article  CAS  PubMed  Google Scholar 

  66. Moysidis SN, Thanos A, Vavvas DG (2012) Mechanisms of inflammation in proliferative vitreoretinopathy: from bench to bedside. Mediat Inflamm 2012:815937

    Article  Google Scholar 

  67. Weichel ED, Colyer MH (2008) Combat ocular trauma and systemic injury. Curr Opin Ophthalmol 19:519–525

    Article  PubMed  Google Scholar 

  68. Pastor JC, de la Rua ER, Martin F (2002) Proliferative vitreoretinopathy: risk factors and pathobiology. Prog Retin Eye Res 21:127–144

    Article  PubMed  Google Scholar 

  69. Snead DR, James S, Snead MP (2008) Pathological changes in the vitreoretinal junction 1: epiretinal membrane formation. Eye (Lond) 22:1310–1317

    Article  CAS  Google Scholar 

  70. Charteris DG, Sethi CS, Lewis GP, Fisher SK (2002) Proliferative vitreoretinopathy-developments in adjunctive treatment and retinal pathology. Eye (Lond) 16:369–374

    Article  CAS  Google Scholar 

  71. Erakgun T, Egrilmez S (2009) Surgical outcomes of transconjunctival sutureless 23-gauge vitrectomy with silicone oil injection. Indian J Ophthalmol 57:105–109

    Article  PubMed  PubMed Central  Google Scholar 

  72. Shah CP, Ho AC, Regillo CD, Fineman MS, Vander JF, Brown GC (2008) Short-term outcomes of 25-gauge vitrectomy with silicone oil for repair of complicated retinal detachment. Retina 28:723–728

    Article  PubMed  Google Scholar 

  73. Riemann CD, Miller DM, Foster RE, Petersen MR (2007) Outcomes of transconjunctival sutureless 25-gauge vitrectomy with silicone oil infusion. Retina 27:296–303

    Article  PubMed  Google Scholar 

  74. Schaal S, Sherman MP, Barr CC, Kaplan HJ (2011) Primary retinal detachment repair: comparison of 1-year outcomes of four surgical techniques. Retina 31:1500–1504

    Article  PubMed  Google Scholar 

  75. Yao Y, Jiang L, Wang ZJ, Zhang MN (2006) Scleral buckling procedures for longstanding or chronic rhegmatogenous retinal detachment with subretinal proliferation. Ophthalmology 113:821–825

    Article  PubMed  Google Scholar 

  76. Storey P, Alshareef R, Khuthaila M, London N, Leiby B, DeCroos C, Kaiser R, Wills PVRSG (2014) Pars plana vitrectomy and scleral buckle versus pars plana vitrectomy alone for patients with rhegmatogenous retinal detachment at high risk for proliferative vitreoretinopathy. Retina 34:1945–1951

    Article  PubMed  Google Scholar 

  77. Quiram PA, Gonzales CR, Hu W, Gupta A, Yoshizumi MO, Kreiger AE, Schwartz SD (2006) Outcomes of vitrectomy with inferior retinectomy in patients with recurrent rhegmatogenous retinal detachments and proliferative vitreoretinopathy. Ophthalmology 113:2041–2047

    Article  PubMed  Google Scholar 

  78. Tsui I, Schubert HD (2009) Retinotomy and silicone oil for detachments complicated by anterior inferior proliferative vitreoretinopathy. Br J Ophthalmol 93:1228–1233

    Article  CAS  PubMed  Google Scholar 

  79. Tan HS, Mura M, Oberstein SY, de Smet MD (2010) Primary retinectomy in proliferative vitreoretinopathy. Am J Ophthalmol 149:447–452

    Article  PubMed  Google Scholar 

  80. Joussen AM, Rizzo S, Kirchhof B, Schrage N, Li X, Lente C, Hilgers RD, Group HSOS (2011) Heavy silicone oil versus standard silicone oil in as vitreous tamponade in inferior PVR (HSO Study): interim analysis. Acta Ophthalmol 89:e483–e489

    Article  PubMed  Google Scholar 

  81. Boscia F, Furino C, Recchimurzo N, Besozzi G, Sborgia G, Sborgia C (2008) Oxane HD vs silicone oil and scleral buckle in retinal detachment with proliferative vitreoretinopathy and inferior retinal breaks. Graefes Arch Clin Exp Ophthalmol 246:943–948

    Article  CAS  PubMed  Google Scholar 

  82. Kralinger MT, Stolba U, Velikay M, Egger S, Binder S, Wedrich A, Haas A, Parel JM, Kieselbach GF (2010) Safety and feasibility of a novel intravitreal tamponade using a silicone oil/acetyl-salicylic acid suspension for proliferative vitreoretinopathy: first results of the Austrian Clinical Multicenter Study. Graefes Arch Clin Exp Ophthalmol 248:1193–1198

    Article  PubMed  Google Scholar 

  83. Ahmadieh H, Feghhi M, Tabatabaei H, Shoeibi N, Ramezani A, Mohebbi MR (2008) Triamcinolone acetonide in silicone-filled eyes as adjunctive treatment for proliferative vitreoretinopathy: a randomized clinical trial. Ophthalmology 115:1938–1943

    Article  PubMed  Google Scholar 

  84. Yamakiri K, Sakamoto T, Noda Y, Nakahara M, Ogino N, Kubota T, Yokoyama M, Furukawa M, Ishibashi T (2008) One-year results of a multicenter controlled clinical trial of triamcinolone in pars plana vitrectomy. Graefes Arch Clin Exp Ophthalmol 246:959–966

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Chen W, Chen H, Hou P, Fok A, Hu Y, Lam DS (2011) Midterm results of low-dose intravitreal triamcinolone as adjunctive treatment for proliferative vitreoretinopathy. Retina 31:1137–1142

    Article  CAS  PubMed  Google Scholar 

  86. Dehghan MH, Ahmadieh H, Soheilian M, Azarmina M, Moradian S, Ramezani AR, Tavallal A, Naghibozakerin J (2010) Effect of oral prednisolone on visual outcomes and complications after scleral buckling. Eur J Ophthalmol 20:419–423

    Article  PubMed  Google Scholar 

  87. Reibaldi M, Russo A, Longo A, Bonfiglio V, Uva MG, Gagliano C, Toro MD, Avitabile T (2013) Rhegmatogenous retinal detachment with a high risk of proliferative vitreoretinopathy treated with episcleral surgery and an intravitreal dexamethasone 0.7-mg implant. Case Rep Ophthalmol 4:79–83

    Article  PubMed  PubMed Central  Google Scholar 

  88. Banerjee PJ, Bunce C, Charteris DG (2013) Ozurdex (a slow-release dexamethasone implant) in proliferative vitreoretinopathy: study protocol for a randomised controlled trial. Trials 14:358

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Kumar A, Nainiwal S, Choudhary I, Tewari HK, Verma LK (2002) Role of daunorubicin in inhibiting proliferative vitreoretinopathy after retinal detachment surgery. Clin Exp Ophthalmol 30:348–351

    Article  PubMed  Google Scholar 

  90. Wiedemann P, Hilgers RD, Bauer P, Heimann K (1998) Adjunctive daunorubicin in the treatment of proliferative vitreoretinopathy: results of a multicenter clinical trial. Daunomycin Study Group. Am J Ophthalmol 126:550–559

    Article  CAS  PubMed  Google Scholar 

  91. Asaria RH, Kon CH, Bunce C, Charteris DG, Wong D, Khaw PT, Aylward GW (2001) Adjuvant 5-fluorouracil and heparin prevents proliferative vitreoretinopathy: results from a randomized, double-blind, controlled clinical trial. Ophthalmology 108:1179–1183

    Article  CAS  PubMed  Google Scholar 

  92. Charteris DG, Aylward GW, Wong D, Groenewald C, Asaria RH, Bunce C, Group PVRS (2004) A randomized controlled trial of combined 5-fluorouracil and low-molecular-weight heparin in management of established proliferative vitreoretinopathy. Ophthalmology 111:2240–2245

    Article  PubMed  Google Scholar 

  93. Wickham L, Bunce C, Wong D, McGurn D, Charteris DG (2007) Randomized controlled trial of combined 5-fluorouracil and low-molecular-weight heparin in the management of unselected rhegmatogenous retinal detachments undergoing primary vitrectomy. Ophthalmology 114:698–704

    Article  CAS  PubMed  Google Scholar 

  94. Fekrat S, de Juan E Jr, Campochiaro PA (1995) The effect of oral 13-cis-retinoic acid on retinal redetachment after surgical repair in eyes with proliferative vitreoretinopathy. Ophthalmology 102:412–418

    Article  CAS  PubMed  Google Scholar 

  95. Chang YC, Hu DN, Wu WC (2008) Effect of oral 13-cis-retinoic acid treatment on postoperative clinical outcome of eyes with proliferative vitreoretinopathy. Am J Ophthalmol 146:440–446

    Article  CAS  PubMed  Google Scholar 

  96. Hsu J, Khan MA, Shieh WS, Chiang A, Maguire JI, Park CH, Garg SJ, Ho AC, Kaiser RS (2016) Effect of serial intrasilicone oil bevacizumab injections in eyes with recurrent proliferative vitreoretinopathy retinal detachment. Am J Ophthalmol 161:65–70.e62

    Article  CAS  PubMed  Google Scholar 

  97. Mandava N, Blackburn P, Paul DB, Wilson MW, Read SB, Alspaugh E, Tritz R, Barber JR, Robbins JM, Kruse CA (2002) Ribozyme to proliferating cell nuclear antigen to treat proliferative vitreoretinopathy. Invest Ophthalmol Vis Sci 43:3338–3348

    PubMed  Google Scholar 

  98. Schiff WM, Hwang JC, Ober MD, Olson JL, Dhrami-Gavazi E, Barile GR, Chang S, Mandava N (2007) Safety and efficacy assessment of chimeric ribozyme to proliferating cell nuclear antigen to prevent recurrence of proliferative vitreoretinopathy. Arch Ophthalmol 125:1161–1167

    Article  CAS  PubMed  Google Scholar 

  99. Khan MA, Brady CJ, Kaiser RS (2015) Clinical management of proliferative vitreoretinopathy: an update. Retina 35:165–175

    Article  PubMed  Google Scholar 

  100. Charteris DG (1995) Proliferative vitreoretinopathy: pathobiology, surgical management, and adjunctive treatment. Br J Ophthalmol 79:953–960

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Garweg JG, Tappeiner C, Halberstadt M (2013) Pathophysiology of proliferative vitreoretinopathy in retinal detachment. Surv Ophthalmol 58:321–329

    Article  PubMed  Google Scholar 

  102. Pennock S, Haddock LJ, Eliott D, Mukai S, Kazlauskas A (2014) Is neutralizing vitreal growth factors a viable strategy to prevent proliferative vitreoretinopathy? Prog Retin Eye Res 40:16–34

    Article  CAS  PubMed  Google Scholar 

  103. Nagasaki H, Shinagawa K, Mochizuki M (1998) Risk factors for proliferative vitreoretinopathy. Prog Retin Eye Res 17:77–98

    Article  CAS  PubMed  Google Scholar 

  104. Pastor JC, Rojas J, Pastor-Idoate S, Di Lauro S, Gonzalez-Buendia L, Delgado-Tirado S (2015) Proliferative vitreoretinopathy: a new concept of disease pathogenesis and practical consequences. Prog Retin Eye Res 51:125. https://doi.org/10.1016/j.preteyeres.2015.07.005

    Article  PubMed  Google Scholar 

  105. Laqua H, Machemer R (1975) Glial cell proliferation in retinal detachment (massive periretinal proliferation). Am J Ophthalmol 80:602–618

    Article  CAS  PubMed  Google Scholar 

  106. Machemer R, Laqua H (1975) Pigment epithelium proliferation in retinal detachment (massive periretinal proliferation). Am J Ophthalmol 80:1–23

    Article  CAS  PubMed  Google Scholar 

  107. Laqua H (1975) Massive periretinal proliferation (MPP) IV. Pre- and subretinal proliferation of glial tissue in experimental retinal detachment. Mod Probl Ophthalmol 15:235–245

    CAS  PubMed  Google Scholar 

  108. Baudouin C, Hofman P, Brignole F, Bayle J, Loubiere R, Gastaud P (1991) Immunocytology of cellular components in vitreous and subretinal fluid from patients with proliferative vitreoretinopathy. Ophthalmologica 203:38–46

    Article  CAS  PubMed  Google Scholar 

  109. Wiedemann P, Weller M (1988) The pathophysiology of proliferative vitreoretinopathy. Acta Ophthalmol Suppl 189:3–15

    CAS  PubMed  Google Scholar 

  110. Charteris DG, Hiscott P, Grierson I, Lightman SL (1992) Proliferative vitreoretinopathy. Lymphocytes in epiretinal membranes. Ophthalmology 99:1364–1367

    Article  CAS  PubMed  Google Scholar 

  111. Charteris DG, Hiscott P, Robey HL, Gregor ZJ, Lightman SL, Grierson I (1993) Inflammatory cells in proliferative vitreoretinopathy subretinal membranes. Ophthalmology 100:43–46

    Article  CAS  PubMed  Google Scholar 

  112. Morescalchi F, Duse S, Gambicorti E, Romano MR, Costagliola C, Semeraro F (2013) Proliferative vitreoretinopathy after eye injuries: an overexpression of growth factors and cytokines leading to a retinal keloid. Mediat Inflamm 2013:269787

    Article  CAS  Google Scholar 

  113. Casaroli-Marano RP, Pagan R, Vilaro S (1999) Epithelial-mesenchymal transition in proliferative vitreoretinopathy: intermediate filament protein expression in retinal pigment epithelial cells. Invest Ophthalmol Vis Sci 40:2062–2072

    CAS  PubMed  Google Scholar 

  114. Wu WC, Kao YH, Hu DN (2000) Relationship between outcome of proliferative vitreoretinopathy and results of tissue culture of excised preretinal membranes. Kaohsiung J Med Sci 16:614–619

    CAS  PubMed  Google Scholar 

  115. Anderson DH, Stern WH, Fisher SK, Erickson PA, Borgula GA (1983) Retinal detachment in the cat: the pigment epithelial-photoreceptor interface. Invest Ophthalmol Vis Sci 24:906–926

    CAS  PubMed  Google Scholar 

  116. Lee SC, Kwon OW, Seong GJ, Kim SH, Ahn JE, Kay ED (2001) Epitheliomesenchymal transdifferentiation of cultured RPE cells. Ophthalmic Res 33:80–86

    Article  CAS  PubMed  Google Scholar 

  117. Stocks SZ, Taylor SM, Shiels IA (2001) Transforming growth factor-beta1 induces alpha-smooth muscle actin expression and fibronectin synthesis in cultured human retinal pigment epithelial cells. Clin Exp Ophthalmol 29:33–37

    Article  CAS  PubMed  Google Scholar 

  118. Glaser BM, Cardin A, Biscoe B (1987) Proliferative vitreoretinopathy. The mechanism of development of vitreoretinal traction. Ophthalmology 94:327–332

    Article  CAS  PubMed  Google Scholar 

  119. Hiscott P, Sheridan C, Magee RM, Grierson I (1999) Matrix and the retinal pigment epithelium in proliferative retinal disease. Prog Retin Eye Res 18:167–190

    Article  CAS  PubMed  Google Scholar 

  120. Agrawal RN, He S, Spee C, Cui JZ, Ryan SJ, Hinton DR (2007) In vivo models of proliferative vitreoretinopathy. Nat Protoc 2:67–77

    Article  CAS  PubMed  Google Scholar 

  121. Chiba C (2014) The retinal pigment epithelium: an important player of retinal disorders and regeneration. Exp Eye Res 123:107–114

    Article  CAS  PubMed  Google Scholar 

  122. Guerin CJ, Hu L, Scicli G, Scicli AG (2001) Transforming growth factor beta in experimentally detached retina and periretinal membranes. Exp Eye Res 73:753–764

    Article  CAS  PubMed  Google Scholar 

  123. Hinton DR, He S, Jin ML, Barron E, Ryan SJ (2002) Novel growth factors involved in the pathogenesis of proliferative vitreoretinopathy. Eye (Lond) 16:422–428

    Article  CAS  Google Scholar 

  124. Elner SG, Elner VM, Jaffe GJ, Stuart A, Kunkel SL, Strieter RM (1995) Cytokines in proliferative diabetic retinopathy and proliferative vitreoretinopathy. Curr Eye Res 14:1045–1053

    Article  CAS  PubMed  Google Scholar 

  125. Desmouliere A, Geinoz A, Gabbiani F, Gabbiani G (1993) Transforming growth factor-beta 1 induces alpha-smooth muscle actin expression in granulation tissue myofibroblasts and in quiescent and growing cultured fibroblasts. J Cell Biol 122:103–111

    Article  CAS  PubMed  Google Scholar 

  126. Desmouliere A, Gabbiani G (1995) Myofibroblast differentiation during fibrosis. Exp Nephrol 3:134–139

    CAS  PubMed  Google Scholar 

  127. Desmouliere A (1995) Factors influencing myofibroblast differentiation during wound healing and fibrosis. Cell Biol Int 19:471–476

    Article  CAS  PubMed  Google Scholar 

  128. Tomasek JJ, Gabbiani G, Hinz B, Chaponnier C, Brown RA (2002) Myofibroblasts and mechano-regulation of connective tissue remodelling. Nat Rev Mol Cell Biol 3:349–363

    Article  CAS  PubMed  Google Scholar 

  129. Gabbiani G (2003) The myofibroblast in wound healing and fibrocontractive diseases. J Pathol 200:500–503

    Article  CAS  PubMed  Google Scholar 

  130. Baudouin C, Fredj-Reygrobellet D, Brignole F, Negre F, Lapalus P, Gastaud P (1993) Growth factors in vitreous and subretinal fluid cells from patients with proliferative vitreoretinopathy. Ophthalmic Res 25:52–59

    Article  CAS  PubMed  Google Scholar 

  131. Cassidy L, Barry P, Shaw C, Duffy J, Kennedy S (1998) Platelet derived growth factor and fibroblast growth factor basic levels in the vitreous of patients with vitreoretinal disorders. Br J Ophthalmol 82:181–185

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Lei H, Hovland P, Velez G, Haran A, Gilbertson D, Hirose T, Kazlauskas A (2007) A potential role for PDGF-C in experimental and clinical proliferative vitreoretinopathy. Invest Ophthalmol Vis Sci 48:2335–2342

    Article  PubMed  Google Scholar 

  133. Pennock S, Rheaume MA, Mukai S, Kazlauskas A (2011) A novel strategy to develop therapeutic approaches to prevent proliferative vitreoretinopathy. Am J Pathol 179:2931–2940

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Cui J, Lei H, Samad A, Basavanthappa S, Maberley D, Matsubara J, Kazlauskas A (2009) PDGF receptors are activated in human epiretinal membranes. Exp Eye Res 88:438–444

    Article  CAS  PubMed  Google Scholar 

  135. Lee H, O’Meara SJ, O’Brien C, Kane R (2007) The role of gremlin, a BMP antagonist, and epithelial-to-mesenchymal transition in proliferative vitreoretinopathy. Invest Ophthalmol Vis Sci 48:4291–4299

    Article  PubMed  Google Scholar 

  136. Hill TP, Spater D, Taketo MM, Birchmeier W, Hartmann C (2005) Canonical Wnt/beta-catenin signaling prevents osteoblasts from differentiating into chondrocytes. Dev Cell 8:727–738

    Article  CAS  PubMed  Google Scholar 

  137. Umazume K, Tsukahara R, Liu L, Fernandez de Castro JP, McDonald K, Kaplan HJ, Tamiya S (2014) Role of retinal pigment epithelial cell beta-catenin signaling in experimental proliferative vitreoretinopathy. Am J Pathol 184:1419–1428

    Article  CAS  PubMed  Google Scholar 

  138. Chen Z, Shao Y, Li X (2015) The roles of signaling pathways in epithelial-to-mesenchymal transition of PVR. Mol Vis 21:706–710

    CAS  PubMed  PubMed Central  Google Scholar 

  139. Yang S, Li H, Li M, Wang F (2015) Mechanisms of epithelial-mesenchymal transition in proliferative vitreoretinopathy. Discov Med 20:207–217

    PubMed  Google Scholar 

  140. Chen X, Xiao W, Wang W, Luo L, Ye S, Liu Y (2014) The complex interplay between ERK1/2, TGFbeta/Smad, and Jagged/Notch signaling pathways in the regulation of epithelial-mesenchymal transition in retinal pigment epithelium cells. PLoS One 9:e96365

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Parrales A, Lopez E, Lee-Rivera I, Lopez-Colome AM (2013) ERK1/2-dependent activation of mTOR/mTORC1/p70S6K regulates thrombin-induced RPE cell proliferation. Cell Signal 25:829–838

    Article  CAS  PubMed  Google Scholar 

  142. Yokoyama K, Kimoto K, Itoh Y, Nakatsuka K, Matsuo N, Yoshioka H, Kubota T (2012) The PI3K/Akt pathway mediates the expression of type I collagen induced by TGF-beta2 in human retinal pigment epithelial cells. Graefes Arch Clin Exp Ophthalmol 250:15–23

    Article  CAS  PubMed  Google Scholar 

  143. Cheng HC, Ho TC, Chen SL, Lai HY, Hong KF, Tsao YP (2008) Troglitazone suppresses transforming growth factor beta-mediated fibrogenesis in retinal pigment epithelial cells. Mol Vis 14:95–104

    CAS  PubMed  PubMed Central  Google Scholar 

  144. Li H, Wang H, Wang F, Gu Q, Xu X (2011) Snail involves in the transforming growth factor beta1-mediated epithelial-mesenchymal transition of retinal pigment epithelial cells. PLoS One 6:e23322

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Gamulescu MA, Chen Y, He S, Spee C, Jin M, Ryan SJ, Hinton DR (2006) Transforming growth factor beta2-induced myofibroblastic differentiation of human retinal pigment epithelial cells: regulation by extracellular matrix proteins and hepatocyte growth factor. Exp Eye Res 83:212–222

    Article  CAS  PubMed  Google Scholar 

  146. Lei H, Rheaume MA, Kazlauskas A (2010) Recent developments in our understanding of how platelet-derived growth factor (PDGF) and its receptors contribute to proliferative vitreoretinopathy. Exp Eye Res 90:376–381

    Article  CAS  PubMed  Google Scholar 

  147. Li M, Li H, Liu X, Xu D, Wang F (2014) MicroRNA-29b regulates TGF-beta1-mediated epithelial-mesenchymal transition of retinal pigment epithelial cells by targeting AKT2. Exp Cell Res 345:115. https://doi.org/10.1016/j.yexcr.2014.09.026

    Article  CAS  PubMed  Google Scholar 

  148. Palma-Nicolas JP, Lopez-Colome AM (2013) Thrombin induces slug-mediated E-cadherin transcriptional repression and the parallel up-regulation of N-cadherin by a transcription-independent mechanism in RPE cells. J Cell Physiol 228:581–589

    Article  CAS  PubMed  Google Scholar 

  149. Bastiaans J, van Meurs JC, van Holten-Neelen C, Nagtzaam NM, van Hagen PM, Chambers RC, Hooijkaas H, Dik WA (2013) Thrombin induces epithelial-mesenchymal transition and collagen production by retinal pigment epithelial cells via autocrine PDGF-receptor signaling. Invest Ophthalmol Vis Sci 54:8306–8314

    Article  CAS  PubMed  Google Scholar 

  150. Bastiaans J, van Meurs JC, van Holten-Neelen C, Nijenhuis MS, Kolijn-Couwenberg MJ, van Hagen PM, Kuijpers RW, Hooijkaas H, Dik WA (2013) Factor Xa and thrombin stimulate proinflammatory and profibrotic mediator production by retinal pigment epithelial cells: a role in vitreoretinal disorders? Graefes Arch Clin Exp Ophthalmol 251:1723–1733

    Article  PubMed  Google Scholar 

  151. Lei H, Kazlauskas A (2014) A reactive oxygen species-mediated, self-perpetuating loop persistently activates platelet-derived growth factor receptor alpha. Mol Cell Biol 34:110–122

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Chen HC, Zhu YT, Chen SY, Tseng SC (2012) Wnt signaling induces epithelial-mesenchymal transition with proliferation in ARPE-19 cells upon loss of contact inhibition. Lab Investig 92:676–687

    Article  CAS  PubMed  Google Scholar 

  153. Kita T, Hata Y, Miura M, Kawahara S, Nakao S, Ishibashi T (2007) Functional characteristics of connective tissue growth factor on vitreoretinal cells. Diabetes 56:1421–1428

    Article  CAS  PubMed  Google Scholar 

  154. Chen YJ, Tsai RK, Wu WC, He MS, Kao YH, Wu WS (2012) Enhanced PKCdelta and ERK signaling mediate cell migration of retinal pigment epithelial cells synergistically induced by HGF and EGF. PLoS One 7:e44937

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Pennock S, Haddock LJ, Mukai S, Kazlauskas A (2014) Vascular endothelial growth factor acts primarily via platelet-derived growth factor receptor alpha to promote proliferative vitreoretinopathy. Am J Pathol 184:3052–3068

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Carrington L, McLeod D, Boulton M (2000) IL-10 and antibodies to TGF-beta2 and PDGF inhibit RPE-mediated retinal contraction. Invest Ophthalmol Vis Sci 41:1210–1216

    CAS  PubMed  Google Scholar 

  157. Connor TB Jr, Roberts AB, Sporn MB, Danielpour D, Dart LL, Michels RG, de Bustros S, Enger C, Kato H, Lansing M et al (1989) Correlation of fibrosis and transforming growth factor-beta type 2 levels in the eye. J Clin Invest 83:1661–1666

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Kita T, Hata Y, Arita R, Kawahara S, Miura M, Nakao S, Mochizuki Y, Enaida H, Goto Y, Shimokawa H, Hafezi-Moghadam A, Ishibashi T (2008) Role of TGF-beta in proliferative vitreoretinal diseases and ROCK as a therapeutic target. Proc Natl Acad Sci U S A 105:17504–17509

    Article  PubMed  PubMed Central  Google Scholar 

  159. Chen X, Xiao W, Liu X, Zeng M, Luo L, Wu M, Ye S, Liu Y (2014) Blockade of Jagged/Notch pathway abrogates transforming growth factor beta2-induced epithelial-mesenchymal transition in human retinal pigment epithelium cells. Curr Mol Med 14:523–534

    Article  CAS  PubMed  Google Scholar 

  160. Sonoda S, Nagineni CN, Kitamura M, Spee C, Kannan R, Hinton DR (2014) Ceramide inhibits connective tissue growth factor expression by human retinal pigment epithelial cells. Cytokine 68:137–140

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  161. Liang CM, Tai MC, Chang YH, Chen YH, Chen CL, Lu DW, Chen JT (2011) Glucosamine inhibits epithelial-to-mesenchymal transition and migration of retinal pigment epithelium cells in culture and morphologic changes in a mouse model of proliferative vitreoretinopathy. Acta Ophthalmol 89:e505–e514

    Article  PubMed  Google Scholar 

  162. Choi K, Lee K, Ryu SW, Im M, Kook KH, Choi C (2012) Pirfenidone inhibits transforming growth factor-beta1-induced fibrogenesis by blocking nuclear translocation of Smads in human retinal pigment epithelial cell line ARPE-19. Mol Vis 18:1010–1020

    CAS  PubMed  PubMed Central  Google Scholar 

  163. Oshima Y, Sakamoto T, Hisatomi T, Tsutsumi C, Ueno H, Ishibashi T (2002) Gene transfer of soluble TGF-beta type II receptor inhibits experimental proliferative vitreoretinopathy. Gene Ther 9:1214–1220

    Article  CAS  PubMed  Google Scholar 

  164. Lei H, Velez G, Hovland P, Hirose T, Gilbertson D, Kazlauskas A (2009) Growth factors outside the PDGF family drive experimental PVR. Invest Ophthalmol Vis Sci 50:3394–3403

    Article  PubMed  Google Scholar 

  165. Xiao W, Chen X, Liu X, Luo L, Ye S, Liu Y (2014) Trichostatin A, a histone deacetylase inhibitor, suppresses proliferation and epithelial-mesenchymal transition in retinal pigment epithelium cells. J Cell Mol Med 18:646–655

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  166. Lei H, Velez G, Cui J, Samad A, Maberley D, Matsubara J, Kazlauskas A (2010) N-acetylcysteine suppresses retinal detachment in an experimental model of proliferative vitreoretinopathy. Am J Pathol 177:132–140

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. Kusaka K, Kothary PC, Del Monte MA (1998) Modulation of basic fibroblast growth factor effect by retinoic acid in cultured retinal pigment epithelium. Curr Eye Res 17:524–530

    Article  CAS  PubMed  Google Scholar 

  168. Umazume K, Liu L, Scott PA, de Castro JP, McDonald K, Kaplan HJ, Tamiya S (2013) Inhibition of PVR with a tyrosine kinase inhibitor, dasatinib, in the swine. Invest Ophthalmol Vis Sci 54:1150–1159

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Ocular Trauma Task Area, US Army Institute of Surgical Research, JBSA Fort Sam Houston, Houston, TX, USA

    Whitney A. Greene, Ramesh R. Kaini & Heuy-Ching Wang

Authors
  1. Whitney A. Greene
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ramesh R. Kaini
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Heuy-Ching Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Heuy-Ching Wang .

Editor information

Editors and Affiliations

  1. National Institutes of Health NEI, Bethesda, MD, USA

    Kapil Bharti

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Greene, W.A., Kaini, R.R., Wang, HC. (2019). Utility of Induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelium for an In Vitro Model of Proliferative Vitreoretinopathy. In: Bharti, K. (eds) Pluripotent Stem Cells in Eye Disease Therapy. Advances in Experimental Medicine and Biology, vol 1186. Springer, Cham. https://doi.org/10.1007/978-3-030-28471-8_2

Download citation

Publish with us

Policies and ethics

Search

Navigation