Advertisement

Eye Platelet-Rich Plasma (E-PRP) for Corneal Regeneration

  • Alejandra E. RodríguezEmail author
  • Jorge L. Alió
Chapter
Part of the Essentials in Ophthalmology book series (ESSENTIALS)

Abstract

After the alteration or injury of the conjunctival or corneal tissue, a biological process of regeneration occurs to restore that damaged ocular surface. This is a complex process involving the epithelial stem cells of the cornea and the conjunctiva since they are responsible for homeostasis and the regeneration of the ocular surface, as well as growth factors, cytokines and elements of the extracellular matrix.

But there are situations in which by the severity of the damage or by the inability of the body itself to resolve the situation, administration of treatments is necessary to solve the problem. In this aspect, the administration of blood products as a therapeutic option has acquired great prominence, due to its biological composition and its ability to induce the regeneration of affected tissues.

In this chapter we analyse the different blood derivatives used in ophthalmology, going deep into platelet-rich plasma (E-PRP). Its composition is reviewed in detail, as cell counts of platelets, red blood cells and leukocytes, as well as the different growth factors and adhesion proteins. The methods of obtaining the main autologous preparations are also indicated, and the clinical applications of the different autologous blood derivatives are discussed and compared among them to obtain relevant conclusions. We analyse how differences in the composition of each of them can affect the corneal regeneration process.

Keywords

PRP E-PRP Platelet-rich plasma Corneal regeneration Autologous Tissue regeneration Eye drops Growth factors 

Notes

Compliance with Ethical Requirements

Conflict of Interest

Alejandra E. Rodríguez and Jorge L. Alio declare that they have no conflict of interest.

Informed Consent

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all patients for being included in the study.

No animal studies were carried out by the authors for this chapter.

References

  1. 1.
    Garg A, Sheppard JD, Donnenfeld ED, Meyer D, Mehta CK. Ojo seco y otros trastornos de la superficie ocular: diagnóstico y tratamiento en xero-dacriología. Madrid. España: Editorial Médica Panamericana, S.A.; 2008. 472 p.Google Scholar
  2. 2.
    Cárdenas Díaz T, Capote Cabrera A, Benítez Merino M d C, Noriega Martínez JL, Montero Díaz E, Hormigó Puertas IF. Medicina regenerativa y superficie ocular. Rev Cuba Oftalmol. 2012;25(1):104–18.Google Scholar
  3. 3.
    Pikuła M, Langa P, Kosikowska P, Trzonkowski P. Stem cells and growth factors in wound healing. Postep Hig Med Dosw. 2015;69:874–85.CrossRefGoogle Scholar
  4. 4.
    Coursey TG, de Paiva CS. Managing Sjögren’s syndrome and non-Sjögren syndrome dry eye with anti-inflammatory therapy. Clin Ophthalmol. 2014;8:1447–58.PubMedPubMedCentralGoogle Scholar
  5. 5.
    Tsubota K, Satake Y, Ohyama M, Toda I, Takano Y, Ono M, et al. Surgical reconstruction of the ocular surface in advanced ocular cicatricial pemphigoid and Stevens-Johnson syndrome. Am J Ophthalmol. 1996;122(1):38–52.CrossRefGoogle Scholar
  6. 6.
    Hick S, Demers PE, Brunette I, La C, Mabon M, Duchesne B. Amniotic membrane transplantation and fibrin glue in the management of corneal ulcers and perforations: a review of 33 cases. Cornea. 2005;24(4):369–77.PubMedCrossRefGoogle Scholar
  7. 7.
    Nakamura T, Inatomi T, Sotozono C, Koizumi N, Kinoshita S. Ocular surface reconstruction using stem cell and tissue engineering. Prog Retin Eye Res. 2015;51:187–207.PubMedCrossRefGoogle Scholar
  8. 8.
    Alio J, Arnalich-Montiel F, Rodriguez A. The role of ‘eye platelet rich plasma’ (E-PRP) for wound healing in ophthalmology. Curr Pharm Biotechnol. 2012;13(7):1257–65.PubMedCrossRefGoogle Scholar
  9. 9.
    Alio JL, Rodriguez AE, WróbelDudzińska D. Eye platelet-rich plasma in the treatment of ocular surface disorders. Curr Opin Ophthalmol. 2015;26(4):325–32.PubMedCrossRefGoogle Scholar
  10. 10.
    Nugent RB, Lee GA. Ophthalmic use of blood-derived products. Surv Ophthalmol. 2015;60(5):406–34.CrossRefGoogle Scholar
  11. 11.
    Ribatti D, Crivellato E. Giulio Bizzozero and the discovery of platelets. Leuk Res. 2007;31(10):1339–41.PubMedCrossRefPubMedCentralGoogle Scholar
  12. 12.
    Rivadeneyra L, Ivani PC, Schattner M, Pozner RG. Así comienza la vida plaquetaria: un viaje desde los megacariocitos medulares a las plaquetas circulantes. Acta Bioquímica Clínica Latinoam. 2016;50(2):233–45.Google Scholar
  13. 13.
    López Farré A, Macaya C. Plaqueta: Fisiologia de la activacion y la inhibicion. Rev Española Cardiol Supl. 2013;13(SUPPL.2):2–7.Google Scholar
  14. 14.
    Farndale RW, Sixma JJ, Barnes MJ, De Groot PG. The role of collagen in thrombosis and hemostasis. J Thromb Haemost. 2004;2(4):561–73.PubMedCrossRefPubMedCentralGoogle Scholar
  15. 15.
    Flores-Rivera OI, Ramírez-Morales K, Meza-Márquez JM, Nava-López JA. Fisiología de la coagulación. Rev Mex Anestesiol. 2014;37:282–386.Google Scholar
  16. 16.
    Xu W, Wang TY, Becker RC. Enfermedades hematologicas: desde dentro del corazon. Rev Esp Cardiol. 2011;64(7):606–13.PubMedCrossRefPubMedCentralGoogle Scholar
  17. 17.
    Hidalgo, Mesa CJ, Cepero Rodríguez I, Berrios Águila JE, Ulloa Quintanilla FO, Polanco Rodríguez F. Infarto cerebral: complicaciones y causas de muerte. Rev Cuba Med Mil. 2005;34(1):1–3.Google Scholar
  18. 18.
    Smyth SS, Mcever RP, Weyrich AS, Morrell CN, Hoffman MR, Arepally GM, et al. Platelet functions beyond hemostasis. J Thromb Haemost. 2009;7(11):1759–66.CrossRefGoogle Scholar
  19. 19.
    González-Villalva A. Sangre y Hematopoyesis. In: Kierszenbaum AL, Tres LL, editors. Histología y Biología Celular. Barcelona, España: Elsevier España, S.L; 2012. p. 168–201.Google Scholar
  20. 20.
    Spinelli SL, Maggirwar SB, Blumberg N, Phipps RP. Nuclear emancipation: a platelet tour de force. Sci Signal. 2010;3(144):pe37.PubMedCrossRefPubMedCentralGoogle Scholar
  21. 21.
    Anitua E, Andia I, Ardanza B, Nurden P, Nurden AT. Autologous platelets as a source of proteins for healing and tissue regeneration. Thromb Haemost. 2004;91(1):4–15.PubMedCrossRefPubMedCentralGoogle Scholar
  22. 22.
    Nurden AT. Platelets, inflammation and tissue regeneration. Thromb Haemost. 2011;105(SUPPL.1):13–33.Google Scholar
  23. 23.
    Marx RE. Platelet-rich plasma: evidence to support its use. J Oral Maxillofac Surg. 2004;62:489–96.PubMedCrossRefPubMedCentralGoogle Scholar
  24. 24.
    Nurden AT, Nurden P, Sanchez M, Andia I, Eduardo A. Platelets and wound healing. Front Biosci. 2008;2(i):3532–48.Google Scholar
  25. 25.
    Gawaz M, Vogel S. Platelets in tissue repair: control of apoptosis and interactions with regenerative cells. Blood. 2013;122(15):2550–4.PubMedCrossRefPubMedCentralGoogle Scholar
  26. 26.
    Diago P, Bielsa JMS. Puesta al día en Factores de crecimiento y proteínas que influyen en el crecimiento óseo: aplicaciones en implantología oral. Periodoncia. 2001;11(3):205–16.Google Scholar
  27. 27.
    Barrientos S, Stojadinovic O, Golinko MS, Brem H, Tomic-Canic M. Growth factors and cytokines in wound healing. Wound Repair Regen. 2008;16(5):585–601.PubMedCrossRefPubMedCentralGoogle Scholar
  28. 28.
    Alvarez RH, Kantarjian HM, Cortes JE. Biology of platelet-derived growth factor and its involvement in disease. Mayo Clin Proc. 2006;81(9):1241–57.PubMedCrossRefPubMedCentralGoogle Scholar
  29. 29.
    Beca T, Hernandez G, Morante S, Bascones A. Plasma rico en plaquetas. Una revisión bibliográfica. Av Periodoncia. 2007;19(1):39–52.Google Scholar
  30. 30.
    Kim WJ, Mohan RR, Mohan RR, Wilson SE. Effect of PDGF, IL-alpha, and BMP2/4 on corneal fibroblast chemotaxis: expression of the platelet-derived growth factor system in the cornea. Investig Ophthalmol Vis Sci. 1999;40(7):1364–72.Google Scholar
  31. 31.
    Colciago A, Celotti F, Casati L, Giancola R, Castano SM, Antonini G, et al. In vitro effects of PDGF isoforms (AA, BB, AB and CC) on migration and proliferation of SaOS-2 osteoblasts and on migration of human osteoblasts. Int J Biomed Sci. 2009;5(4):380–9.PubMedPubMedCentralGoogle Scholar
  32. 32.
    Andrae J, Gallini R, Betsholtz C. Role of platelet-derived growth factors in physiology and medicine. Genes Dev. 2008;22(10):1276–312.PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Robson MC, Phillips LG, Thomason A, Robson LE, Pierce GF. Platelet-derived growth factor BB for the treatment of chronic pressure ulcers. Lancet (London, England). 1992;339(8784):23–5.CrossRefGoogle Scholar
  34. 34.
    Pierce GF, Tarpley JE, Allman RM, Goode PS, Serdar CM, Morris AB, et al. Tissue repair processes in healing chronic pressure ulcers treated with recombinant platelet-derived growth factor BB. Am J Pathol. 1994;145(6):1399.PubMedPubMedCentralGoogle Scholar
  35. 35.
    Pierce GF, Tarpley JE, Tseng J, Bready J, Chang D, Kenney WC, et al. Detection of platelet-derived growth factor (PDGF)-AA in actively healing human wounds treated with recombinant PDGF-BB and absence of PDGF in chronic nonhealing wounds. J Clin Invest. 1995;96(3):1336–50.PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Smiell JM, Wieman TJ, Steed DL, Perry BH, Sampson AR, Schwab BH. Efficacy and safety of becaplermin (recombinant human platelet-derived growth factor-BB) in patients with nonhealing, lower extremity diabetic ulcers: a combined analysis of four randomized studies. Wound Repair Regen. 1999;7(5):335–46.PubMedCrossRefGoogle Scholar
  37. 37.
    Steed DL. Clinical evaluation of recombinant human platelet-derived growth factor for the treatment of lower extremity ulcers. Plast Reconstr Surg. 2006;117(7 Suppl):143S–9S. discussion 150S–151S.PubMedCrossRefGoogle Scholar
  38. 38.
    Sarment DP, Cooke JW, Miller SE, Jin Q, McGuire MK, Kao RT, et al. Effect of rhPDGF-BB on bone turnover during periodontal repair. J Clin Periodontol. 2006;33(2):135–40.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Nevins M, Camelo M, Nevins ML, Schenk RK, Lynch SE. Periodontal regeneration in humans using recombinant human platelet-derived growth factor-BB (rhPDGF-BB) and allogenic bone. J Periodontol. 2003;74(9):1282–92.PubMedCrossRefGoogle Scholar
  40. 40.
    Saika S. TGFbeta pathobiology in the eye. Lab Investig. 2006;86(2):106–15.CrossRefGoogle Scholar
  41. 41.
    Costanza B, Umelo I, Bellier J, Castronovo V, Turtoi A. Stromal modulators of TGF-β in Cancer. J Clin Med. 2017;6(1):7.PubMedCentralCrossRefPubMedGoogle Scholar
  42. 42.
    Stahnke T, Kowtharapu BS, Stachs O, Schmitz K-P, Wurm J, Wree A, et al. Suppression of TGF-β pathway by pirfenidone decreases extracellular matrix deposition in ocular fibroblasts in vitro. PLoS One. 2017;12(2):e0172592.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Il GS, Kim Y-H, Jung J-C, Kim IG, Lee JS, Lee KW, et al. Cyclosporine A inhibits TGF-β2-induced myofibroblasts of primary cultured human pterygium fibroblasts. Biochem Biophys Res Commun. 2016;482(4):1148–53.Google Scholar
  44. 44.
    Wang L, Wu X, Shi T, Lu L. Epidermal growth factor (EGF)-induced corneal epithelial wound healing through nuclear factor κB subtype-regulated CCCTC binding factor (CTCF) activation. J Biol Chem. 2013;288(34):24363–71.PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Hodges RR, Bair JA, Carozza RB, Li D, Shatos MA, Dartt DA. Signaling pathways used by EGF to stimulate conjunctival goblet cell secretion. Exp Eye Res. 2012;103:99–113.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Kenchegowda S, Bazan NG, Bazan HEP. EGF stimulates lipoxin A4 synthesis and modulates repair in corneal epithelial cells through ERK and p38 activation. Investig Ophthalmol Vis Sci. 2011;52(5):2240–9.CrossRefGoogle Scholar
  47. 47.
    Khanbanha N, Atyabi F, Taheri A, Talaie F, Mahbod M, Dinarvand R. Healing efficacy of an EGF impregnated triple gel based wound dressing: in vitro and in vivo studies. Biomed Res Int. 2014;2014:1–10.CrossRefGoogle Scholar
  48. 48.
    Ferrara N, Houck K, Jakeman LYN, Leung DW. Molecular and biological properties of the vascular endothelial growth factor family of proteins. Endocr Rev. 1992;13(1):18–32.PubMedCrossRefGoogle Scholar
  49. 49.
    Yu CQ, Zhang M, Matis KI, Kim C, Rosenblatt MI. Vascular endothelial growth factor mediates corneal nerve repair. Invest Ophthalmol Vis Sci. 2008;49(9):3870–8.PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Duffy AM, Bouchier-hayes DJ, Harmey JH. Vascular endothelial growth factor (VEGF) and its role in non-endothelial cells: autocrine signalling by VEGF. In: VEGF and Cancer. Austin: Landes Bioscience; 2004. p. 133–44.CrossRefGoogle Scholar
  51. 51.
    Stevenson W, Cheng SF, Dastjerdi MH, Ferrari G, Dana R. Corneal neovascularization and the utility of topical VEGF inhibition: ranibizumab (Lucentis) vs bevacizumab (Avastin). Ocul Surf. 2012;10(2):67–83.PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Lucena S, Arocha Piñango CL, Guerrero B. Fibronectin. Structure and functions associated to hemostasis. Review Invest Clin. 2007;48(2):249–62.PubMedGoogle Scholar
  53. 53.
    Pastar I, Stojadinovic O, Yin NC, Ramirez H, Nusbaum AG, Sawaya A, et al. Epithelialization in wound healing: a comprehensive review. Adv Wound Care. 2014;3(7):445–64.CrossRefGoogle Scholar
  54. 54.
    Ljubimov AV, Saghizadeh M. Progress in corneal wound healing. Prog Retin Eye Res. 2015;49:17–45.PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Paniagua R, Manuel N, Pilar S, Manuel A-U, Benito F, Ramón A, Sáez JF. Biología Celular. Madrid: McGraw-Hill – Interamericana de España, S. A. U; 2007. 381 p.Google Scholar
  56. 56.
    Makogonenko E, Tsurupa G, Ingham K, Medved L. Interaction of fibrin(ogen) with fibronectin: further characterization and localization of the fibronectin-binding site. Biochemistry. 2002;41(25):7907–13.PubMedCrossRefGoogle Scholar
  57. 57.
    De La Mata J. Plasma rico en plaquetas: ¿un nuevo tratamiento para el reumatologo? Reumatol Clin. 2013;9(3):166–71.Google Scholar
  58. 58.
    Hartwig D, Harloff S, Liu L, Schlenke P, Wedel T, Geerling G. Epitheliotrophic capacity of a growth factor preparation produced from platelet concentrates on corneal epithelial cells: a potential agent for the treatment of ocular surface defects? Transfusion. 2004;44(12):1724–31.PubMedCrossRefGoogle Scholar
  59. 59.
    Hartwig D, Herminghaus P, Wedel T, Liu L, Schlenke P, Dibbelt L, et al. Topical treatment of ocular surface defects: comparison of the epitheliotrophic capacity of fresh frozen plasma and serum on corneal epithelial cells in an in vitro cell culture model. Transfus Med. 2005;15(2):107–13.PubMedCrossRefGoogle Scholar
  60. 60.
    Liu L, Hartwig D, Harloff S, Herminghaus P, Wedel T, Kasper K, et al. Corneal epitheliotrophic capacity of three different blood-derived preparations. Investig Ophthalmol Vis Sci. 2006;47(6):2438–44.CrossRefGoogle Scholar
  61. 61.
    Anitua E. Plasma rich in growth factors: preliminary results of use in the preparation of future sites for implants. Int J Oral Maxillofac Implants. 1999;14(4):529–35.PubMedGoogle Scholar
  62. 62.
    Anitua E, Andía I, Sanchez M, Azofra J, del Mar Zalduendo M, de la Fuente M, et al. Autologous preparations rich in growth factors promote proliferation and induce VEGF and HGF production by human tendon cells in culture. J Orthop Res. 2005;23(2):281–6.PubMedCrossRefGoogle Scholar
  63. 63.
    Anitua E, Sánchez M, Zalduendo MM, De La Fuente M, Prado R, Orive G, et al. Fibroblastic response to treatment with different preparations rich in growth factors. Cell Prolif. 2009;42(2):162–70.PubMedCrossRefGoogle Scholar
  64. 64.
    Anitua E, de la Fuente M, Muruzabal F, Riestra A, Merayo-Lloves J, Orive G. Plasma rich in growth factors (PRGF) eye drops stimulates scarless regeneration compared to autologous serum in the ocular surface stromal fibroblasts. Exp Eye Res. 2015;135:118–26.PubMedCrossRefGoogle Scholar
  65. 65.
    Anitua E, Sanchez M, Merayo-Lloves J, de La Fuente M, Muruzabal F, Orive G. Plasma rich in growth factors (PRGF-Endoret) stimulates proliferation and migration of primary keratocytes and conjunctival fibroblasts and inhibits and reverts TGF-β1-induced myodifferentiation. Investig Ophthalmol Vis Sci. 2011;52(9):6066–73.CrossRefGoogle Scholar
  66. 66.
    Freire V, Andollo N, Etxebarria J, Durán JA, Morales M-C. In vitro effects of three blood derivatives on human corneal epithelial cells. Invest Ophthalmol Vis Sci. 2012;53(9):5571–8.PubMedCrossRefGoogle Scholar
  67. 67.
    Freire V, Andollo N, Etxebarria J, Hernáez-Moya R, Durán JA, Morales M-C. Corneal wound healing promoted by 3 blood derivatives: an in vitro and in vivo comparative study. Cornea. 2014;33(6):614–20.PubMedCrossRefGoogle Scholar
  68. 68.
    Anitua E, Muruzabal F, Alcalde I, Merayo-Lloves J, Orive G. Plasma rich in growth factors (PRGF-Endoret) stimulates corneal wound healing and reduces haze formation after PRK surgery. Exp Eye Res. 2013;115:153–61.PubMedCrossRefGoogle Scholar
  69. 69.
    Etxebarria J, Sanz-Lázaro S, Hernáez-Moya R, Freire V, Durán JA, Morales MC, et al. Serum from plasma rich in growth factors regenerates rabbit corneas by promoting cell proliferation, migration, differentiation, adhesion and limbal stemness. Acta Ophthalmol. 2017.  https://doi.org/10.1111/aos.13371.PubMedCrossRefGoogle Scholar
  70. 70.
    Anitua E, Sánchez M, Nurden AT, Zalduendo MM, De la Fuente M, Azofra J, et al. Platelet-released growth factors enhance the secretion of hyaluronic acid and induce hepatocyte growth factor production by synovial fibroblasts from arthritic patients. Rheumatology. 2007;46(12):1769–72.PubMedCrossRefGoogle Scholar
  71. 71.
    Assirelli E, Filardo G, Mariani E, Kon E, Roffi A, Vaccaro F, et al. Effect of two different preparations of platelet-rich plasma on synoviocytes. Knee Surgery, Sport Traumatol Arthrosc. 2015;23(9):2690–703.CrossRefGoogle Scholar
  72. 72.
    Beitzel K, McCarthy MB, Russell RP, Apostolakos J, Cote MP, Mazzocca AD. Learning about PRP using cell-based models. Muscles Ligaments Tendons J. 2014;4(1):38–45.PubMedPubMedCentralGoogle Scholar
  73. 73.
    Masoudi EA, Ribas J, Kaushik G, Leijten J, Khademhosseini A. Platelet-rich blood derivatives for stem cell-based tissue engineering and regeneration. Curr Stem Cell Reports. 2016;2(1):33–42.CrossRefGoogle Scholar
  74. 74.
    López-García JS, García-Lozano I, Rivas L, Ramírez N, Méndez MT, Raposo R. Stability of growth factors in autologous serum eyedrops after long-term storage. Curr Eye Res. 2015;3683(November):1–7.CrossRefGoogle Scholar
  75. 75.
    Poon AC, Geerling G, Dart JK, Fraenkel GE, Daniels JT. Autologous serum eyedrops for dry eyes and epithelial defects: clinical and in vitro toxicity studies. Br J Ophthalmol. 2001;85(10):1188–97.PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Pinarli F, Okten G, Beden U, Fışgın T, Kefeli M, Kara N, et al. Keratinocyte growth factor-2 and autologous serum potentiate the regenerative effect of mesenchymal stem cells in cornea damage in rats. Int J Ophthalmol. 2014;7(2):211–9.PubMedPubMedCentralGoogle Scholar
  77. 77.
    López-García JS, García-Lozano I, Rivas L, Giménez C, Acera A, Suárez-Cortés T. Effects of autologous serum eye drops on conjunctival expression of MUC5AC in patients with ocular surface disorders. Cornea. 2016;35(3):336–41.PubMedCrossRefGoogle Scholar
  78. 78.
    Dohan DM, Choukroun J, Diss A, Dohan SL, Dohan AJJ, Mouhyi J, et al. Platelet-rich fibrin (PRF): a second-generation platelet concentrate. Part III: leucocyte activation: a new feature for platelet concentrates? Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006;101(3):51–5.CrossRefGoogle Scholar
  79. 79.
    El-Sharkawy H, Kantarci A, Deady J, Hasturk H, Liu H, Alshahat M, et al. Platelet-rich plasma: growth factors and pro- and anti-inflammatory properties. J Periodontol. 2007;78(4):661–9.PubMedCrossRefGoogle Scholar
  80. 80.
    Mazzocca AD, Mccarthy BR, Intravia J, Beitzel KA, Apostolakos J, Cote MP, et al. An in vitro evaluation of the anti-inflammatory effects of platelet-rich plasma, ketorolac, and methylprednisolone. Arthrosc J Arthrosc Relat Surg. 2013;29(4):675–83.CrossRefGoogle Scholar
  81. 81.
    Schär MO, Diaz-Romero J, Kohl S, Zumstein MA, Nesic D. Platelet-rich concentrates differentially release growth factors and induce cell migration in vitro. Clin Orthop Relat Res. 2015;473(5):1635–43.PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    Anitua E, Zalduendo MM, Prado R, Alkhraisat MH, Orive G. Morphogen and proinflammatory cytokine release kinetics from PRGF-Endoret fibrin scaffolds: evaluation of the effect of leukocyte inclusion. J Biomed Mater Res - Part A. 2015;103(3):1011–20.CrossRefGoogle Scholar
  83. 83.
    Anitua E, Zalduendo M, Troya M, Padilla S, Orive G. Leukocyte inclusion within a platelet rich plasma-derived fibrin scaffold stimulates a more pro-inflammatory environment and alters fibrin properties. PLoS One. 2015;10(3):1–19.CrossRefGoogle Scholar
  84. 84.
    Anitua E, Muruzabal F, De la Fuente M, Merayo-Lloves J, Orive G. Effects of heat-treatment on plasma rich in growth factors-derived autologous eye drop. Exp Eye Res. 2014;119:27–34.PubMedCrossRefGoogle Scholar
  85. 85.
    Anitua E, Muruzabal F, de la Fuente M, Riestra A, Merayo-Lloves J, Orive G. PRGF exerts more potent proliferative and anti-inflammatory effects than autologous serum on a cell culture inflammatory model. Exp Eye Res. 2016;151:115–21.PubMedCrossRefGoogle Scholar
  86. 86.
    Stenwall PA, Bergström M, Seiron P, Sellberg F, Olsson T, Knutson F, et al. Improving the anti-inflammatory effect of serum eye drops using allogeneic serum permissive for regulatory T cell induction. Acta Ophthalmol. 2015;93(7):654–7.PubMedCrossRefGoogle Scholar
  87. 87.
    Chiang C-C, Chen W-L, Lin J-M, Tsai Y-Y. Allogeneic serum eye drops for the treatment of persistent corneal epithelial defect. Eye. 2009;23(2):290–3.CrossRefGoogle Scholar
  88. 88.
    Chiang C-C, Lin J-M, Chen W-L, Tsai Y-Y. Allogeneic serum eye drops for the treatment of severe dry eye in patients with chronic graft-versus-host disease. Cornea. 2007;26(7):861–3.PubMedCrossRefGoogle Scholar
  89. 89.
    Na K-S, Kim MS. Allogeneic serum eye drops for the treatment of dry eye patients with chronic graft-versus-host disease. J Ocul Pharmacol Ther. 2012;28(5):479–83.PubMedPubMedCentralCrossRefGoogle Scholar
  90. 90.
    Tang YQ, Yeaman MR, Selsted ME. Antimicrobial peptides from human platelets. Infect Immun. 2002;70(12):6524–33.PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Tohidnezhad M, Varoga D, Podschun R, Wruck CJ, Seekamp A, Brandenburg LO, et al. Thrombocytes are effectors of the innate immune system releasing human beta defensin-3. Injury. 2011;42(7):682–6.PubMedCrossRefPubMedCentralGoogle Scholar
  92. 92.
    Drago L, Bortolin M, Vassena C, Taschieri S, Del Fabbro M. Antimicrobial activity of pure platelet-rich plasma against microorganisms isolated from oral cavity. BMC Microbiol. 2013;13:47.PubMedPubMedCentralCrossRefGoogle Scholar
  93. 93.
    Anitua E, Muruzabal F, Orive G. Antimicrobial properties of plasma rich in growth factors (PRGF- ENDORET) technology. Sci Microb Pathog Commun Curr Res Technol Adv. 2011(1):414–21.Google Scholar
  94. 94.
    Li H, Hamza T, Tidwell JE, Clovis N, Li B. Unique antimicrobial effects of platelet-rich plasma and its efficacy as a prophylaxis to prevent implant-associated spinal infection. Adv Healthc Mater. 2013;2(9):1277–84.PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Bielecki T, Gazdzik TS, Szczepanski T. Benefit of percutaneous injection of autologous platelet-leukocyte-rich gel in patients with delayed union and nonunion. Eur Surg Res. 2008;40(3):289–96.PubMedCrossRefPubMedCentralGoogle Scholar
  96. 96.
    Dohan Ehrenfest DM, Andia I, Zumstein MA, Zhang C-Q, Pinto NR, Bielecki T. Classification of platelet concentrates (platelet-rich plasma-PRP, platelet-rich fibrin-PRF) for topical and infiltrative use in orthopedic and sports medicine: current consensus, clinical implications and perspectives. Muscles Ligaments Tendons J. 2014;4(1):3–9.PubMedPubMedCentralGoogle Scholar
  97. 97.
    Marx RE. Platelet-rich plasma (PRP): what is PRP and what is not PRP? Implant Dent. 2001;10(4):225–8.PubMedCrossRefPubMedCentralGoogle Scholar
  98. 98.
    Alio JL, Abad M, Artola A, Rodriguez-Prats JL, Pastor S, Ruiz-Colecha J. Use of autologous platelet-rich plasma in the treatment of dormant corneal ulcers. Ophthalmology. 2007;114(7):1286–94.PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Alio JL, Pastor S, Ruiz-Colecha J, Rodriguez A, Artola A. Treatment of ocular surface syndrome after LASIK with autologous platelet-rich plasma. J Refract Surg. 2007;23(6):617–9.PubMedCrossRefPubMedCentralGoogle Scholar
  100. 100.
    Alio JL, Colecha JR, Pastor S, Rodriguez A, Artola A. Symptomatic dry eye treatment with autologous platelet-rich plasma. Ophthalmic Res. 2007;39(3):124–9.PubMedCrossRefPubMedCentralGoogle Scholar
  101. 101.
    Alio JL, Rodriguez AE, Martinez LM, Rio AL. Autologous fibrin membrane combined with solid platelet-rich plasma in the Management of Perforated Corneal Ulcers. JAMA Ophthalmol. 2013;131(6):745 751.CrossRefGoogle Scholar
  102. 102.
    Alio JL, Rodriguez AE, Martinez LM. Bovine pericardium membrane (Tutopatch) combined with solid platelet-rich plasma for the management of perforated corneal ulcers. Cornea. 2013;32(5):619–24.PubMedCrossRefPubMedCentralGoogle Scholar
  103. 103.
    Moreno R, Carreño MG, María J, Herreros A, Romero Garrido JA, López-Sánchez P. Plasma rico en plaquetas: actualización de los sistemas empleados para su obtención. Farm Hosp [Internet]. 2016 [cited 2017 May 8];40(5):385–93. Available from: http://scielo.isciii.es/pdf/fh/v40n5/05original05.pdf.
  104. 104.
    Anitua E, Muruzabal F, Pino A, Merayo-Lloves J, Orive G. Biological stability of plasma rich in growth factors eye drops after storage of 3 months. Cornea. 2013;32(10):1380–6.PubMedCrossRefPubMedCentralGoogle Scholar
  105. 105.
    Geerling G, Maclennan S, Hartwig D. Autologous serum eye drops for ocular surface disorders. Br J Ophthalmol. 2004;88(11):1467–74.PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    Movahedan H, Ghassemifar V. Treatment of persistent corneal epithelial defect with autologous serum. Asian J Ophthalmol. 2006;8(6):236–41.Google Scholar
  107. 107.
    López-García JS, García-Lozano I, Rivas L, Martínez-Garchitorena J. Use of autologous serum in ophthalmic practice. Arch Soc Esp Oftalmol. 2007;82(1):9–20.PubMedCrossRefPubMedCentralGoogle Scholar
  108. 108.
    Tananuvat N, Daniell M, Sullivan LJ, Yi Q, McKelvie P, McCarty DJ, et al. Controlled study of the use of autologous serum in dry eye patients. Cornea. 2001;20(8):802–6.PubMedCrossRefPubMedCentralGoogle Scholar
  109. 109.
    Lagnado R, King AJ, Donald F, Dua HSA. Protocol for low contamination risk of autologous serum drops in the management of ocular surface disorders. Br J Ophthalmol. 2004;88(4):464–5.PubMedPubMedCentralCrossRefGoogle Scholar
  110. 110.
    Noble BA, Loh RS, MacLennan S, Pesudovs K, Reynolds A, Bridges LR, et al. Comparison of autologous serum eye drops with conventional therapy in a randomised controlled crossover trial for ocular surface disease. Br J Ophthalmol. 2004;88(5):647–52.PubMedPubMedCentralCrossRefGoogle Scholar
  111. 111.
    von Hofsten J, Egardt M, Zetterberg M. The use of autologous serum for the treatment of ocular surface disease at a Swedish tertiary referral center. Int Med Case Rep J. 2016;9:47–54.CrossRefGoogle Scholar
  112. 112.
    López-García JS, García-Lozano I, Rivas L, Ramírez N, Raposo R, Méndez MT. Autologous serum eye drops diluted with sodium hyaluronate: clinical and experimental comparative study. Acta Ophthalmol. 2014;92(1):22–9.CrossRefGoogle Scholar
  113. 113.
    Semeraro F, Forbice E, Braga O, Bova A, Di Salvatore A, Azzolini C. Evaluation of the efficacy of 50% autologous serum eye drops in different ocular surface pathologies. Biomed Res Int. 2014;2014:826970.PubMedPubMedCentralGoogle Scholar
  114. 114.
    Gus PI, Marinho D, Zelanis S, Belló-Klein A, Locatelli C, Nicola F, et al. A case-control study on the oxidative balance of 50% autologous serum eye drops. Oxidative Med Cell Longev. 2016;2016:9780193.CrossRefGoogle Scholar
  115. 115.
    Liu L, Hartwig D, Harloff S, Herminghaus P, Wedel T, Geerling G. An optimised protocol for the production of autologous serum eyedrops. Graefes Arch Clin Exp Ophthalmol. 2005;243(7):706–14.PubMedCrossRefGoogle Scholar
  116. 116.
    Fox RI, Chan R, Michelson JB, Belmont JB, Michelson PE. Beneficial effect of artificial tears made with autologous serum in patients with keratoconjunctivitis sicca. Arthritis Rheum. 1984;27(4):459–61.PubMedCrossRefGoogle Scholar
  117. 117.
    Viso E, Gude F, Rodríguez-Ares MT. The association of meibomian gland dysfunction and other common ocular diseases with dry eye: a population-based study in Spain. Cornea. 2011;30(1):1–6.PubMedCrossRefGoogle Scholar
  118. 118.
    Al-Saedi Z, Zimmerman A, Bachu RD, Dey S, Shah Z, Baugh R, et al. Dry eye disease: present challenges in the management and future trends. Curr Pharm Des. 2016;22(28):4470–90.PubMedCrossRefGoogle Scholar
  119. 119.
    Muñoz-Hernández AM, Santos-Bueso E, Cuiña-Sardiña R, Díaz-Valle D, Gegúndez-Fernández JA, Benítez-del-Castillo JM. New therapies for neurotrophic keratitis. Arch Soc Esp Oftalmol. 2016;91(3):105–7.PubMedCrossRefGoogle Scholar
  120. 120.
    Rosenthal AR, Harbury C, Egbert PR, Rubenstein E. Use of a platelet-fibrinogen-thrombin mixture as a corneal adhesive: experiments with sutureless lamellar keratoplasty in the rabbit. Inv Ophthalmol. 1975;14(November):872–5.Google Scholar
  121. 121.
    Ralph R, Doane M, Dohlman C. Clinical experience with a mobile ocular perfusion pump. Arch Ophthalmol. 1975;93(10):1039–43.PubMedCrossRefPubMedCentralGoogle Scholar
  122. 122.
    Semeraro F, Forbice E, Nascimbeni G, Taglietti M, Romano V, Guerra G, et al. Effect of autologous serum eye drops in patients with Sjögren syndrome-related dry eye: clinical and in vivo confocal microscopy evaluation of the ocular surface. In Vivo (Brooklyn). 2016;30(6):931–8.CrossRefGoogle Scholar
  123. 123.
    Soni NG, Jeng BH. Blood-derived topical therapy for ocular surface diseases. Br J Ophthalmol. 2016;100(1):22–7.PubMedCrossRefPubMedCentralGoogle Scholar
  124. 124.
    Noda-Tsuruya T, Asano-Kato N, Toda I, Tsubota K. Autologous serum eye drops for dry eye after LASIK. J Refract Surg. 2006;22(1):61–6.PubMedCrossRefGoogle Scholar
  125. 125.
    Pan Q, Angelina A, Marrone M, Stark WJ, Akpek EK. Autologous serum eye drops for dry eye. Pan Q, editor. Cochrane Database Syst Rev 2017;2.  https://doi.org/10.1002/14651858. CD009327. pub3. Review.
  126. 126.
    Anitua E, Muruzabal F, Tayebba A, Riestra A, Perez VL, Merayo-Lloves J, et al. Autologous serum and plasma rich in growth factors in ophthalmology: preclinical and clinical studies. Acta Ophthalmol. 2015;93(8):e605–14.PubMedCrossRefGoogle Scholar
  127. 127.
    Alio JL, Rodriguez AE, Ferreira-Oliveira R, Wróbel-Dudzińska D, Abdelghany AA. Treatment of dry eye disease with autologous platelet-rich plasma: a prospective, interventional, non-randomized study. Ophthalmol Ther. 2017;6(2):285–93.PubMedPubMedCentralCrossRefGoogle Scholar
  128. 128.
    Alio JL, Rodriguez AE, Abdelghany AA, Oliveira RF. Autologous platelet-rich plasma eye drops for the treatment of post-LASIK chronic ocular surface syndrome. J Ophthalmol. 2017.  https://doi.org/10.1155/2017/2457620.CrossRefGoogle Scholar
  129. 129.
    Alio JL, Rodriguez AE, De Arriba P, Gisbert S, Abdelghany AA. Treatment with platelet-rich plasma of surgically related dormant corneal ulcers. Eur J Ophthalmol. 2018;28(5):515–20.PubMedCrossRefPubMedCentralGoogle Scholar
  130. 130.
    Ortuño-Prados VJ, Alio JL. Tratamiento de úlcera corneal neurotrófica con plasma rico en plaquetas y Tutopatch®. Arch Soc Esp Oftalmol. 2011;86(4):121–3.PubMedCrossRefGoogle Scholar
  131. 131.
    Arnalich F, Rodriguez AE, Luque-Rio A, Alio JL. Solid platelet rich plasma in corneal surgery. Ophthalmol Ther. 2016;5(1):31–45.PubMedPubMedCentralCrossRefGoogle Scholar
  132. 132.
    Javaloy J, Alió JL, Rodriguez AE, Vega A, Muñoz G. Effect of platelet-rich plasma in nerve regeneration after LASIK. J Refract Surg. 2013;29(3):213–9.PubMedCrossRefGoogle Scholar
  133. 133.
    Kim KM, Shin Y-T, Kim HK. Effect of autologous platelet-rich plasma on persistent corneal epithelial defect after infectious keratitis. Jpn J Ophthalmol. 2012;56(6):544–50.PubMedCrossRefGoogle Scholar
  134. 134.
    Lee JH, Kim MJ, Ha SW, Kim HK. Autologous platelet-rich plasma eye drops in the treatment of recurrent corneal erosions. Korean J Ophthalmol. 2016;30(2):101–7.PubMedPubMedCentralCrossRefGoogle Scholar
  135. 135.
    Avila MY. Restoration of human lacrimal function following platelet-rich plasma injection. Cornea. 2014;33(1):18–21.PubMedCrossRefGoogle Scholar
  136. 136.
    Figueroa MS, Govetto A, De Arriba-Palomero P. Short-term results of platelet-rich plasma as adjuvant to 23-G vitrectomy in the treatment of high myopic macular holes. Eur J Ophthalmol. 2015;26(5):491–6.PubMedCrossRefGoogle Scholar
  137. 137.
    Del Cid RMDA, Escoriaza IMDE. Subconjunctival application of regenerative factor-rich plasma for the treatment of ocular alkali burns. Eur J Ophthalmol. 2009;19(6):909–15.CrossRefGoogle Scholar
  138. 138.
    Anitua E, Alkhraisat MH, Orive G. Perspectives and challenges in regenerative medicine using plasma rich in growth factors. J Control Release. 2012;157(1):29–38.PubMedCrossRefGoogle Scholar
  139. 139.
    Anitua E, Sánchez M, Orive G, Padilla S. A biological therapy to osteoarthritis treatment using platelet-rich plasma. Expert Opin Biol Ther. 2013;13(8):1161–72.PubMedCrossRefGoogle Scholar
  140. 140.
    Anitua E, Pino A, Martinez N, Orive G, Berridi D. The effect of plasma rich in growth factors on pattern hair loss: a pilot study. Dermatol Surg. 2017;43(5):658–70.PubMedCrossRefGoogle Scholar
  141. 141.
    Lopez-Plandolit S, Morales M-C, Freire V, Grau AE, Duran JA. Efficacy of plasma rich in growth factors for the treatment of dry eye. Cornea. 2011;30(12):1312–7.PubMedCrossRefGoogle Scholar
  142. 142.
    Merayo-Lloves J, Sanchez-Avila RM, Riestra AC, Anitua E, Begoña L, Orive G, et al. Safety and efficacy of autologous plasma rich in growth factors eye drops for the treatment of evaporative dry eye. Ophthalmic Res. 2016;56(2):68–73.PubMedCrossRefGoogle Scholar
  143. 143.
    Merayo-Lloves J, Sanchez RM, Riestra AC, Anitua E, Begoña L, Orive G, et al. Autologous plasma rich in growth factors eyedrops in refractory cases of ocular surface disorders. Ophthalmic Res. 2016;55(2):53–61.CrossRefGoogle Scholar
  144. 144.
    Sanchez-Avila RM, Merayo-Lloves J, Riestra AC, Fernandez-Vega Cueto L, Anitua E, Begoña L, et al. Treatment of patients with neurotrophic keratitis stages 2 and 3 with plasma rich in growth factors (PRGF-Endoret) eye-drops. Int Ophthalmol. 2017.  https://doi.org/10.1007/s10792-017-0582-7.PubMedCrossRefGoogle Scholar
  145. 145.
    Tanidir ST, Yuksel N, Altintas O, Yildiz DK, Sener E, Caglar Y. The effect of subconjunctival platelet-rich plasma on corneal epithelial wound healing. Cornea. 2010;29(6):664–9.PubMedCrossRefGoogle Scholar
  146. 146.
    Mazzocca AD. Platelet-rich plasma differs according to preparation method and human variability. J Bone Jt Surg. 2012;94(4):308.CrossRefGoogle Scholar
  147. 147.
    Urzua C a., Vasquez DH, Huidobro A, Hernandez H, Alfaro J. Randomized double-blind clinical trial of autologous serum versus artificial tears in dry eye syndrome. Curr Eye Res. 2012;37(8):684–8.PubMedCrossRefGoogle Scholar
  148. 148.
    Celebi ARC, Ulusoy C, Mirza GE. The efficacy of autologous serum eye drops for severe dry eye syndrome: a randomized double-blind crossover study. Graefes Arch Clin Exp Ophthalmol. 2014;252(4):619–26.PubMedCrossRefGoogle Scholar
  149. 149.
    Stellos K, Kopf S, Paul A, Marquardt JU, Gawaz M, Huard J, et al. Platelets in regeneration. Semin Thromb Hemost. 2010;36(2):175–84.PubMedCrossRefGoogle Scholar
  150. 150.
    Amable PR, Carias RBV, Teixeira MVT, da Cruz Pacheco I, Corrêa do Amaral RJF, Granjeiro JM, et al. Platelet-rich plasma preparation for regenerative medicine: optimization and quantification of cytokines and growth factors. Stem Cell Res Ther. 2013;4(3):67.PubMedPubMedCentralCrossRefGoogle Scholar
  151. 151.
    Pochini A de C, Antonioli E, Bucci DZ, Sardinha LR, Andreoli CV, Ferretti M, et al. Analysis of cytokine profile and growth factors in platelet-rich plasma obtained by open systems and commercial columns. Einstein (São Paulo). 2016;14(3):391–7.CrossRefGoogle Scholar
  152. 152.
    Dhurat R, Sukesh M. Principles and methods of preparation of platelet-rich plasma: a review and author’s perspective. J Cutan Aesthet Surg. 2014;7(4):189–97.PubMedPubMedCentralCrossRefGoogle Scholar
  153. 153.
    Zhong W, Sumita Y, Ohba S, Kawasaki T, Nagai K, Ma G, et al. In vivo comparison of the bone regeneration capability of human bone marrow concentrates vs. platelet-rich plasma. PLoS One. 2012;7(7):e40833.PubMedPubMedCentralCrossRefGoogle Scholar
  154. 154.
    McCarrel TM, Minas T, Fortier LA. Optimization of leukocyte concentration in platelet-rich plasma for the treatment of tendinopathy. JBJS-American. 2012;94(19):1–8.CrossRefGoogle Scholar
  155. 155.
    Sundman EA, Cole BJ, Fortier LA. Growth factor and catabolic cytokine concentrations are influenced by the cellular composition of platelet-rich plasma. Am J Sports Med. 2011;39(10):2135–40.PubMedCrossRefGoogle Scholar
  156. 156.
    González M, Arteaga-vizcaíno M, Ruiz A, Briceño O, Quintero M, Atencio R, et al. Niveles del factor de crecimiento derivado de plaquetas en el plasma rico en plaquetas antes y despues de antiagregantes plaquetarios (PDGF levels in platelet-rich plasma before and after anti platelets drugs). Av en Biomed. 2013;2(3):127–36.Google Scholar
  157. 157.
    Weibrich G, Kleis WKG, Hafner G, Hitzler WE. Growth factor levels in platelet-rich plasma and correlations with donor age, sex, and platelet count. J Cranio-Maxillofacial Surg. 2002;30(2):97–102.CrossRefGoogle Scholar
  158. 158.
    Ronci C, Ferraro AS, Lanti A, Missiroli F, Sinopoli S, Del Proposto G, et al. Platelet-rich plasma as treatment for persistent ocular epithelial defects. Transfus Apher Sci. 2015;52(3):300–4.PubMedCrossRefGoogle Scholar
  159. 159.
    González M, Arteaga-Vizcaíno M, Benito M, Benito M. Application of platelet rich plasma (PRP) and its derivatives in dental implantologie and plastic surgery. Investig Clin. 2012;53(4):408–18.Google Scholar
  160. 160.
    Kobayashi Y, Saita Y, Nishio H, Ikeda H, Takazawa Y, Nagao M, et al. Leukocyte concentration and composition in platelet-rich plasma (PRP) influences the growth factor and protease concentrations. J Orthop Sci. 2016;21(5):683–9.PubMedCrossRefGoogle Scholar
  161. 161.
    Yuan N, Wang C, Wang Y, Yu T, Long Y, Zhang X, et al. Preparation of autologous platelet-rich gel for diabetic refractory dermal ulcer and growth factors analysis from it. Chin J Reparative Reconstr Surg. 2008;22(4):468–71.Google Scholar
  162. 162.
    Zimmermann R, Jakubietz R, Jakubietz M, Strasser E, Schlegel A, Wiltfang J, et al. Different preparation methods to obtain platelet components as a source of growth factors for local application. Transfusion. 2001;41(10):1217–24.PubMedCrossRefGoogle Scholar
  163. 163.
    Eppley BL, Woodell JE, Higgins J. Platelet quantification and growth factor analysis from platelet-rich plasma: implications for wound healing. Plast Reconstr Surg. 2004 Nov;114(6):1502–8.PubMedCrossRefGoogle Scholar
  164. 164.
    Ambroziak AM, Szaflik J, Szaflik JP, Ambroziak M, Witkiewicz J, Skopinski P. Immunomodulation on the ocular surface: a review. Cent Eur J Immunol. 2016;41(2):195–208.PubMedPubMedCentralCrossRefGoogle Scholar
  165. 165.
    Castillo TN, Pouliot MA, Kim HJ, Dragoo JL. Comparison of growth factor and platelet concentration from commercial platelet-rich plasma separation systems. Am J Sports Med. 2011;39(2):266–71.PubMedCrossRefGoogle Scholar
  166. 166.
    Grainger DJ, Mosedale DE, Metcalfe JC. TGF-beta in blood: a complex problem. Cytokine Growth Factor Rev. 11(1–2):133–45.Google Scholar
  167. 167.
    Li ZD, Bork JP, Krueger B, Patsenker E, Schulze-Krebs A, Hahn EG, et al. VEGF induces proliferation, migration, and TGF-beta1 expression in mouse glomerular endothelial cells via mitogen-activated protein kinase and phosphatidylinositol 3-kinase. Biochem Biophys Res Commun. 2005;334(4):1049–60.PubMedCrossRefGoogle Scholar
  168. 168.
    Hoeben A, Landuyt B, Highley MS, Wildiers H, Van Oosterom AT, De Bruijn EA. Vascular endothelial growth factor and angiogenesis. Pharmacol Rev. 2004;56(4):549–80.PubMedCrossRefGoogle Scholar
  169. 169.
    Shibuya M. Structure and function of VEGF/VEGF-receptor system involved in angiogenesis. Cell Struct Funct. 2001;26(1):25–35.PubMedCrossRefGoogle Scholar
  170. 170.
    López-Plandolit S, Morales M-C, Freire V, Etxebarría J, Durán J a. Plasma rich in growth factors as a therapeutic agent for persistent corneal epithelial defects. Cornea. 2010;29(8):843–8.PubMedCrossRefGoogle Scholar
  171. 171.
    Blumenstock FA, Valeri CR, Saba TM, Cho E, Melaragno A, Gray A, et al. Progressive loss of fibronectin-mediated opsonic activity in plasma cryoprecipitate with storage. Role of fibronectin fragmentation. Vox Sang. 1988;54(3):129–37.PubMedCrossRefGoogle Scholar
  172. 172.
    Plöderl K, Strasser C, Hennerbichler S, Peterbauer-Scherb A, Gabriel C. Development and validation of a production process of platelet lysate for autologous use. Platelets. 2011;22(3):204–9.PubMedCrossRefGoogle Scholar
  173. 173.
    Nishida T. Translational research in corneal epithelial wound healing. Eye Contact Lens. 2010;36(5):300–4.PubMedCrossRefPubMedCentralGoogle Scholar
  174. 174.
    Klenkler B, Sheardown H, Jones L. Growth factors in the tear film: role in tissue maintenance, wound healing, and ocular pathology. Ocul Surf. 2007;5(3):228–39.PubMedPubMedCentralCrossRefGoogle Scholar
  175. 175.
    Shen EP, Hu F-R, Lo S-C, Chen Y-M, Sun Y-C, Lin C-T, et al. Comparison of corneal epitheliotrophic capacity among different human blood–derived preparations. Cornea. 2011;30(2):208–14.PubMedCrossRefPubMedCentralGoogle Scholar
  176. 176.
    Xiao X, He H, Lin Z, Luo P, He H, Zhou T, et al. Therapeutic effects of epidermal growth factor on benzalkonium chloride–induced dry eye in a mouse model. Investig Opthalmology Vis Sci. 2012;53(1):191–7.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Laboratory of the Research, Development and Innovation Department, Vissum InnovationAlicanteSpain
  2. 2.Professor and Chairman of Ophthalmology, University Miguel HernandezVissum-Instituto Oftalmologico de AlicanteAlicanteSpain

Personalised recommendations