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The upregulation of zinc finger protein 670 and prostaglandin D2 synthase in proliferative vitreoretinopathy

  • Retinal Disorders
  • Published:
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Abstract

Purpose

Proteins in the vitreous play an important role on the induction of proliferative vitreoretinopathy (PVR) after retinal detachment. The aim of this study was to investigate the variation of protein patterns in the vitreous of PVR eyes and examine whether differentially expressed protein levels were expressed in experimental PVR retina.

Methods

Vitreous samples from PVR and macular hole patients were selected for proteomic analysis. The vitreous protein samples were separated by two-dimensional electrophoresis (2-DE). The differentially expressed protein spots in the two groups were excised and subjected to in-gel digestion and identification by electrospray ionization mass spectrometry (ESI-MS) analysis. Two differentially expressed proteins, zinc finger protein 670 (ZFP 670) and prostaglandin D2 synthase (PGD2S), were further validated by immunohistochemical staining and western blotting analysis in the retina of the experimental rabbit PVR model.

Results

In proteome analysis of human vitreous samples, five proteins had increased expression in PVR, including zinc finger protein 670 (ZFP 670), prostaglandin D2 synthase (PGD2S), IgG (Immunoglobulin G) light chain, transthyretin precursor, and haptoglobin precursor. ZFP 670 and PGD2S levels were expressed significantly higher in the experimental PVR retinas than in the control group.

Conclusions

Levels of ZFP 670 and PGD2S were elevated in the vitreous fluid of patients with PVR. In addition, there were higher expressions of ZFP 670 and PGD2S in the experimental PVR retina. This result will expand our knowledge of pathophysiologic characteristics of PVR, and might be helpful for further developing possible treatment on this disorder.

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References

  1. Chignell AH, Fison LG, Davies EW, Hartley RE, Gundry MF (1973) Failure in retinal detachment surgery. Br J Ophthalmol 57:525–530

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  2. Heimann H, Bartz-Schmidt KU, Bornfeld N, Weiss C, Hilgers RD, Foerster MH (2007) Scleral buckling versus primary vitrectomy in rhegmatogenous retinal detachment: a prospective randomized multicenter clinical study. Ophthalmology 114:2142–2154

    Article  PubMed  Google Scholar 

  3. Singer AJ, Clark RA (1999) Cutaneous wound healing. N Engl J Med 341:738–746

    Article  PubMed  CAS  Google Scholar 

  4. Sethi CS, Lewis GP, Fisher SK, Leitner WP, Mann DL, Luthert PJ, Charteris DG (2005) Glial remodeling and neural plasticity in human retinal detachment with proliferative vitreoretinopathy. Invest Ophthalmol Vis Sci 46:329–342

    Article  PubMed  Google Scholar 

  5. Vinores SA, Campochiaro PA, Conway BP (1990) Ultrastructural and electron-immunocytochemical characterization of cells in epiretinal membranes. Invest Ophthalmol Vis Sci 31:14–28

    PubMed  CAS  Google Scholar 

  6. Wiedemann P (1992) Growth factors in retinal diseases: proliferative vitreoretinopathy, proliferative diabetic retinopathy, and retinal degeneration. Surv Ophthalmol 36:373–384

    Article  PubMed  CAS  Google Scholar 

  7. Kon CH, Asaria RH, Occleston NL, Khaw PT, Aylward GW (2000) Risk factors for proliferative vitreoretinopathy after primary vitrectomy: a prospective study. Br J Ophthalmol 84:506–511

    Article  PubMed  CAS  PubMed Central  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  9. 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  PubMed  CAS  Google Scholar 

  10. 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  PubMed  CAS  Google Scholar 

  11. Gorg A, Obermaier C, Boguth G, Harder A, Scheibe B, Wildgruber R, Weiss W (2000) The current state of two-dimensional electrophoresis with immobilized pH gradients. Electrophoresis 21:1037–1053

    Article  PubMed  CAS  Google Scholar 

  12. Hanash SM (2000) Biomedical applications of two-dimensional electrophoresis using immobilized pH gradients: current status. Electrophoresis 21:1202–1209

    Article  PubMed  CAS  Google Scholar 

  13. Matsumoto H, Komori N (2000) Ocular proteomics: cataloging photoreceptor proteins by two-dimensional gel electrophoresis and mass spectrometry. Methods Enzymol 316:492–511

    Article  PubMed  CAS  Google Scholar 

  14. Roepstorff P (1997) Mass spectrometry in protein studies from genome to function. Curr Opin Biotechnol 8:6–13

    Article  PubMed  CAS  Google Scholar 

  15. Yates JR 3rd (1998) Database searching using mass spectrometry data. Electrophoresis 19:893–900

    Article  PubMed  CAS  Google Scholar 

  16. Kristensen DB, Imamura K, Miyamoto Y, Yoshizato K (2000) Mass spectrometric approaches for the characterization of proteins on a hybrid quadrupole time-of-flight (Q-TOF) mass spectrometer. Electrophoresis 21:430–439

    Article  PubMed  CAS  Google Scholar 

  17. Kuo HK, Wu PC, Yang PM, Chen YH, Wu YC, Hu DN (2007) Effects of topoisomerase II inhibitors on retinal pigment epithelium and experimental proliferative vitreoretinopathy. J Ocul Pharmacol Ther 23:14–20

    Article  PubMed  CAS  Google Scholar 

  18. Lee JJ, Park JK, Kim YT, Kwon BM, Kang SG, Yoo YD, Yu YS, Chung H (2002) Effect of 2′-benzoyl-oxycinnamaldehyde on RPE cells in vitro and in an experimental proliferative vitreoretinopathy model. Invest Ophthalmol Vis Sci 43:3117–3124

    PubMed  Google Scholar 

  19. Mandelcorn MS, Machemer R, Fineberg E, Hersch SB (1975) Proliferation and metaplasia of intravitreal retinal pigment epithelium cell autotransplants. Am J Ophthalmol 80:227–237

    Article  PubMed  CAS  Google Scholar 

  20. Fastenberg DM, Diddie KR, Dorey K, Ryan SJ (1982) The role of cellular proliferation in an experimental model of massive periretinal proliferation. Am J Ophthalmol 93:565–572

    Article  PubMed  CAS  Google Scholar 

  21. Yamane K, Minamoto A, Yamashita H, Takamura H, Miyamoto-Myoken Y, Yoshizato K, Nabetani T, Tsugita A, Mishima HK (2003) Proteome analysis of human vitreous proteins. Mol Cell Proteomics 2:1177–1187

    Article  PubMed  CAS  Google Scholar 

  22. Yu J, Liu F, Cui SJ, Liu Y, Song ZY, Cao H, Chen FE, Wang WJ, Sun T, Wang F (2008) Vitreous proteomic analysis of proliferative vitreoretinopathy. Proteomics 8:3667–3678

    Article  PubMed  CAS  Google Scholar 

  23. Ando N, Sen HA, Berkowitz BA, Wilson CA, de Juan E Jr (1994) Localization and quantitation of blood–retinal barrier breakdown in experimental proliferative vitreoretinopathy. Arch Ophthalmol 112:117–122

    Article  PubMed  CAS  Google Scholar 

  24. Little BC, Ambrose VM (1991) Blood–aqueous barrier breakdown associated with rhegmatogenous retinal detachment. Eye (Lond) 5(Pt 1):56–62

    Article  CAS  Google Scholar 

  25. Kon CH, Occleston NL, Aylward GW, Khaw PT (1999) Expression of vitreous cytokines in proliferative vitreoretinopathy: a prospective study. Invest Ophthalmol Vis Sci 40:705–712

    PubMed  CAS  Google Scholar 

  26. 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 

  27. Buehler PW, Abraham B, Vallelian F, Linnemayr C, Pereira CP, Cipollo JF, Jia Y, Mikolajczyk M, Boretti FS, Schoedon G, Alayash AI, Schaer DJ (2009) Haptoglobin preserves the CD163 hemoglobin scavenger pathway by shielding hemoglobin from peroxidative modification. Blood 113:2578–2586

    Article  PubMed  CAS  Google Scholar 

  28. de Kleijn DP, Smeets MB, Kemmeren PP, Lim SK, Van Middelaar BJ, Velema E, Schoneveld A, Pasterkamp G, Borst C (2002) Acute-phase protein haptoglobin is a cell migration factor involved in arterial restructuring. FASEB J 16:1123–1125

    PubMed  Google Scholar 

  29. Padma T, Murty JS, Satapathy M (1980) Haptoglobin pattern in retinal detachments. Indian J Med Res 71:914–917

    PubMed  CAS  Google Scholar 

  30. Chignell AH, Carruthers M, Rahi AH (1971) Clinical, biochemical, and immunoelectrophoretic study of subretinal fluid. Br J Ophthalmol 55:525–532

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  31. Getz RK, Kennedy BG, Mangini NJ (1999) Transthyretin localization in cultured and native human retinal pigment epithelium. Exp Eye Res 68:629–636

    Article  PubMed  CAS  Google Scholar 

  32. Pfeffer BA, Becerra SP, Borst DE, Wong P (2004) Expression of transthyretin and retinol binding protein mRNAs and secretion of transthyretin by cultured monkey retinal pigment epithelium. Mol Vis 10:23–30

    PubMed  CAS  Google Scholar 

  33. Delcourt C, Dupuy AM, Carriere I, Lacroux A, Cristol JP (2005) Albumin and transthyretin as risk factors for cataract: the POLA study. Arch Ophthalmol 123:225–232

    Article  PubMed  Google Scholar 

  34. Duan X, Lu Q, Xue P, Zhang H, Dong Z, Yang F, Wang N (2008) Proteomic analysis of aqueous humor from patients with myopia. Mol Vis 14:370–377

    PubMed  CAS  PubMed Central  Google Scholar 

  35. Mullins RF, Russell SR, Anderson DH, Hageman GS (2000) Drusen associated with aging and age-related macular degeneration contain proteins common to extracellular deposits associated with atherosclerosis, elastosis, amyloidosis, and dense deposit disease. FASEB J 14:835–846

    PubMed  CAS  Google Scholar 

  36. Sandgren O (1995) Ocular amyloidosis, with special reference to the hereditary forms with vitreous involvement. Surv Ophthalmol 40:173–196

    Article  PubMed  CAS  Google Scholar 

  37. Van Aken E, De Letter EA, Veckeneer M, Derycke L, van Enschot T, Geers I, Delanghe S, Delanghe JR (2009) Transthyretin levels in the vitreous correlate with change in visual acuity after vitrectomy. Br J Ophthalmol 93:1539–1545

    Article  PubMed  Google Scholar 

  38. 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  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  40. Elner SG, Elner VM, Pavilack MA, Todd RF 3rd, Mayo-Bond L, Franklin WA, Strieter RM, Kunkel SL, Huber AR (1992) Modulation and function of intercellular adhesion molecule-1 (CD54) on human retinal pigment epithelial cells. Lab Invest 66:200–211

    PubMed  CAS  Google Scholar 

  41. Baudouin C, Fredj-Reygrobellet D, Gordon WC, Baudouin F, Peyman G, Lapalus P, Gastaud P, Bazan NG (1990) Immunohistologic study of epiretinal membranes in proliferative vitreoretinopathy. Am J Ophthalmol 110:593–598

    Article  PubMed  CAS  Google Scholar 

  42. Clausen R, Weller M, Wiedemann P, Heimann K, Hilgers RD, Zilles K (1991) An immunochemical quantitative analysis of the protein pattern in physiologic and pathologic vitreous. Graefes Arch Clin Exp Ophthalmol 229:186–190

    Article  PubMed  CAS  Google Scholar 

  43. Weller M, Clausen R, Bresgen M, Heimann K, Wiedemann P (1990) Immunoglobulin G, complement factor C3 and lymphocytes in proliferative intraocular disorders. Int Ophthalmol 14:277–283

    Article  PubMed  CAS  Google Scholar 

  44. Urade Y, Eguchi N (2002) Lipocalin-type and hematopoietic prostaglandin D synthases as a novel example of functional convergence. Prostaglandins Other Lipid Mediat 68–69:375–382

    Article  PubMed  Google Scholar 

  45. Urade Y, Hayaishi O (2000) Prostaglandin D synthase: structure and function. Vitam Horm 58:89–120

    Article  PubMed  CAS  Google Scholar 

  46. Beuckmann CT, Gordon WC, Kanaoka Y, Eguchi N, Marcheselli VL, Gerashchenko DY, Urade Y, Hayaishi O, Bazan NG (1996) Lipocalin-type prostaglandin D synthase (beta-trace) is located in pigment epithelial cells of rat retina and accumulates within interphotoreceptor matrix. J Neurosci 16:6119–6124

    PubMed  CAS  Google Scholar 

  47. Goh Y, Urade Y, Fujimoto N, Hayaishi O (1987) Content and formation of prostaglandins and distribution of prostaglandin-related enzyme activities in the rat ocular system. Biochim Biophys Acta 921:302–311

    Article  PubMed  CAS  Google Scholar 

  48. Logdberg L, Wester L (2000) Immunocalins: a lipocalin subfamily that modulates immune and inflammatory responses. Biochim Biophys Acta 1482:284–297

    Article  PubMed  CAS  Google Scholar 

  49. Taniguchi H, Mohri I, Okabe-Arahori H, Aritake K, Wada K, Kanekiyo T, Narumiya S, Nakayama M, Ozono K, Urade Y, Taniike M (2007) Prostaglandin D2 protects neonatal mouse brain from hypoxic ischemic injury. J Neurosci 27:4303–4312

    Article  PubMed  CAS  Google Scholar 

  50. Taniguchi H, Mohri I, Okabe-Arahori H, Kanekiyo T, Kagitani-Shimono K, Wada K, Urade Y, Nakayama M, Ozono K, Taniike M (2007) Early induction of neuronal lipocalin-type prostaglandin D synthase after hypoxic–ischemic injury in developing brains. Neurosci Lett 420:39–44

    Article  PubMed  CAS  Google Scholar 

  51. Govoni S, Masoero E, Favalli L, Rozza A, Scelsi R, Viappiani S, Buccellati C, Sala A, Folco G (2001) The Cycloxygenase-2 inhibitor SC58236 is neuroprotective in an in vivo model of focal ischemia in the rat. Neurosci Lett 303:91–94

    Article  PubMed  CAS  Google Scholar 

  52. Kagitani-Shimono K, Mohri I, Oda H, Ozono K, Suzuki K, Urade Y, Taniike M (2006) Lipocalin-type prostaglandin D synthase (beta-trace) is upregulated in the alphaB-crystallin-positive oligodendrocytes and astrocytes in the chronic multiple sclerosis. Neuropathol Appl Neurobiol 32:64–73

    Article  PubMed  CAS  Google Scholar 

  53. Taniike M, Mohri I, Eguchi N, Beuckmann CT, Suzuki K, Urade Y (2002) Perineuronal oligodendrocytes protect against neuronal apoptosis through the production of lipocalin-type prostaglandin D synthase in a genetic demyelinating model. J Neurosci 22:4885–4896

    PubMed  CAS  Google Scholar 

  54. Gerashchenko DY, Beuckmann CT, Marcheselli VL, Gordon WC, Kanaoka Y, Eguchi N, Urade Y, Hayaishi O, Bazan NG (1998) Localization of lipocalin-type prostaglandin D synthase (beta-trace) in iris, ciliary body, and eye fluids. Invest Ophthalmol Vis Sci 39:198–203

    PubMed  CAS  Google Scholar 

  55. Giacomelli S, Leone MG, Grima J, Silvestrini B, Cheng CY (1996) Astrocytes synthesize and secrete prostaglandin D synthetase in vitro. Biochim Biophys Acta 1310:269–276

    Article  PubMed  Google Scholar 

  56. Jaggi GP, Flammer J, Huber AR, Killer HE (2008) Lipocalin-like prostaglandin D synthase in subretinal fluid of detached retinas in humans. Retina 28:858–863

    Article  PubMed  Google Scholar 

  57. Kujawski M, Kortylewski M, Lee H, Herrmann A, Kay H, Yu H (2008) Stat3 mediates myeloid cell-dependent tumor angiogenesis in mice. J Clin Invest 118:3367–3377

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  58. Ganss B, Jheon A (2004) Zinc finger transcription factors in skeletal development. Crit Rev Oral Biol Med 15:282–297

    Article  PubMed  Google Scholar 

  59. Tupler R, Perini G, Green MR (2001) Expressing the human genome. Nature 409:832–833

    Article  PubMed  CAS  Google Scholar 

  60. McConnell BB, Ghaleb AM, Nandan MO, Yang VW (2007) The diverse functions of Kruppel-like factors 4 and 5 in epithelial biology and pathobiology. Bioessays 29:549–557

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  61. Peng H, Du ZW, Zhang JW (2006) Identification and characterization of a novel zinc finger protein (HZF1) gene and its function in erythroid and megakaryocytic differentiation of K562 cells. Leukemia 20:1109–1116

    Article  PubMed  CAS  Google Scholar 

  62. Takahashi Y, Fujioka Y, Takahashi T, Domoto K, Takahashi A, Taniguchi T, Ishikawa Y, Yokoyama M (2005) Chylomicron remnants regulate early growth response factor-1 in vascular smooth muscle cells. Life Sci 77:670–682

    Article  PubMed  CAS  Google Scholar 

  63. 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  PubMed  CAS  PubMed Central  Google Scholar 

  64. Watabe Y, Baba Y, Nakauchi H, Mizota A, Watanabe S (2011) The role of Zic family zinc finger transcription factors in the proliferation and differentiation of retinal progenitor cells. Biochem Biophys Res Commun 415:42–47

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported by grants (NSC 94-2314-B-182A-171, NSC 98-2314-B-182A-032) from the National Science Council, Taiwan, ROC, and a grant (CMRPG891281) from Kaohsiung Chang-Gung Memorial Hospital, Taiwan. The authors are also grateful to the Center for Resources, Research, and Development (Kaohsiung Medical University) for their instrumental support of this work.

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All authors certify that they have NO affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.

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Correspondence to Pei-Chang Wu.

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Kuo, HK., Chen, YH., Huang, F. et al. The upregulation of zinc finger protein 670 and prostaglandin D2 synthase in proliferative vitreoretinopathy. Graefes Arch Clin Exp Ophthalmol 254, 205–213 (2016). https://doi.org/10.1007/s00417-015-3022-2

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