Skip to main content
Log in

Vitreal induzierte RPE-Zell-Traktion

Untersuchung pathologischer Glaskörperproben in einem In-vitro-Kontraktionsmodell

Vitreal-induced RPE cell traction

Investigation of pathological vitreous samples in an in vitro contraction model

  • Originalien
  • Published:
Der Ophthalmologe Aims and scope Submit manuscript

Zusammenfassung

Hintergrund

Zielsetzung dieser Studie war, die Kontraktilität von retinalen Pigmentepithel- (RPE-)Zellen zu quantifizieren, die durch bioaktive Faktoren pathologischer Glaskörperproben induziert wird.

Material und Methoden

Unter Verwendung eines In-vitro-Kontraktionsmodells konnten die Aktivität von Glaskörperproben unterschiedlicher vitreoretinaler Erkrankungen untersucht werden. Dazu wurden transdifferentierte porcine RPE-Zellen auf hemisphärische Typ-I-Kollagen-Gele aufgebracht. Nach Zugabe der Glaskörperproben [physiologisch (n=6); rhegmatogene Ablatio (n=11); proliferative Vitreoretinopathie (PVR, n=10); proliferative diabetische Retinopathie (PDR, n=6)] wurde die induzierte Gelkontraktion bestimmt.

Ergebnisse

Die spezifische Aktivität der unklassifizierten Proben betrug 0,04 (Median, Spannweite, SW: 0–0,08). Glaskörperproben, die von Patienten mit verschiedenen PVR-Stadien gewonnen wurden, wiesen eine spezifische Aktivität von 0,45 (Median, SW: 0,03–1,45) auf. Die Glaskörperproben von rhegmatogen bedingten Netzhautablösungen zeigten eine Aktivität von 0,13 (Median, SW: 0,01–0,93). Die spezifische Aktivität von Glaskörperproben von Patienten mit diabetischer Retinopathie betrug 0,17 (Median, SW: 0,06–0,29). Die mittlere spezifische Aktivität und Gesamtaktivität dieser Gruppen waren signifikant im Vergleich zu den unklassifizierten Proben bzw. den Basiswerten erhöht (p<0,05).

Schlussfolgerung

Pathologische Glaskörperproben unterschiedlicher vitreoretinaler Erkrankungen enthalten ausreichende Mengen von biologisch aktiven Substanzen, die eine Kontraktion von Extrazellulärmatrix induzieren können.

Abstract

Background

The aim of this study was to quantify the contraction of retinal pigment epithelium cells (RPE) induced by bioactive factors in pathological vitreous samples.

Material and methods

Using an in vitro contraction assay, the contraction-stimulating activity of vitreous samples of different vitreoretinal pathologies was evaluated. Transdifferentiated porcine RPE cells were placed on hemispherical type I collagen gel. After exposure to pathological vitreous samples derived from different entities (physiological (n=6), rhegmatogenous retinal detachment (n=11), proliferative vitreoretinopathy (PVR) (=10), proliferative diabetic retinopathy (n=6)) the induced gel contraction was determined.

Results

The specific activity of the unclassified samples was 0.04 (median, range: 0-0.08). Vitreous samples derived from patients diagnosed as having any grade of PVR displayed a specific activity of 0.45 (median, range: 0.03-1.45). Samples removed from patients with rhegmatogenous retinal detachment disclosed a specific activity of 0.13 (median, range: 0.01-0.93). The specific activity of vitreous samples removed from patients with diabetic retinopathy had a specific activity of 0.17 (median, range: 0.06-0.29). The mean specific and total activities of these groups were significantly elevated above the unclassified or baseline values (p<0.05).

Conclusion

Pathological vitreous samples of different vitreoretinal pathologies contain sufficient amounts of biologically active factors to induce extracellular matrix contraction.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Abb. 1
Abb. 2
Abb. 3
Abb. 4

Literatur

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  3. Connor TB jr, Roberts AB, Sporn MB 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  Google Scholar 

  4. Das A, McGuire PG, Eriqat C et al. (1999) Human diabetic neovascular membranes contain high levels of urokinase and metalloproteinase enzymes. Invest Ophthalmol Vis Sci 40: 809–813

    CAS  PubMed  Google Scholar 

  5. Flood M, Gouras P, Kjeldbye H (1980) Growth characteristics and ultrastructure of human retinal pigment epithelium in vitro. Invest Ophthalmol Vis Sci 19: 1309–1320

    CAS  PubMed  Google Scholar 

  6. Grisanti S, Guidry C (1995) Transdifferentiation of retinal pigment epithelial cells from epithelial to mesenchymal phenotype. Invest Ophthalmol Vis Sci 36: 391–405

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  8. Guidry C, McFarland R, Morris R et al. (1992) Collagen gel contraction by cells associated with proliferative vitreoretinopathy. Invest Ophthalmol Vis Sci 33: 2429–2435

    CAS  PubMed  Google Scholar 

  9. Guidry C, Grinnel F (1985) Studies on the mechanism of hydrated collagen gel reorganization by human skin fibroblasts. J Cell Sci 79: 67–81

    CAS  PubMed  Google Scholar 

  10. Hardwick C, Feist R, Morris R et al. (1997) Tractional force generation by porcine müller cells: stimulation by growth factors in human vitreous. Invest Ophthalmol Vis Sci 38: 2053–2063

    CAS  PubMed  Google Scholar 

  11. Hardwick C, Morris R, Witherspoon D et al. (1995) Pathologic human vitreous promotes contraction by fibroblasts. Implications for proliferative vitreoretinopathy. Arch Ophthalmol 113: 1545–1553

    CAS  PubMed  Google Scholar 

  12. Heidenkummer HP, Kampik A (1991) Immunohistochemical localization of epidermal growth factor receptor in a human epiretinal membrane. Graefes Arch Clin Exp Ophthalmol 229: 492–496

    Article  CAS  PubMed  Google Scholar 

  13. Hunt R, Pakalnis V, Choudhury P, Black E (1992) Cytokines and serum cause a2b1 integrin-mediated contraction of collagen gels by cultured retinal pigment epithelial cells. Invest Ophthalmol Vis Sci 35: 955–963

    Google Scholar 

  14. Jerdan JA, Pepose JS, Michels RG et al. (1989) Proliferative vitreoretinopathy membranes. An immunohistochemical study. Ophthalmology 96: 801–810

    CAS  PubMed  Google Scholar 

  15. Kampik A, Kenyon K, Michels R et al. (2005) Epiretinal and vitreous membranes: comparative study of 56 cases. Arch Ophthalmol 25(Suppl 5): 1445–1454

    Google Scholar 

  16. Kupfer T, Ferguson T (1993) A potential pathophysiologic role for a2b1 integrin in human eye diseases involving vitreoretinal traction. FASEB 7: 1401

    Google Scholar 

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

    CAS  PubMed  Google Scholar 

  18. Laqua H, Machemer R (1977) Massive periretinale proliferation. I: Histologie. Ber Dtsch Ophthalmol Ges 74: 357–363

    CAS  Google Scholar 

  19. Lashkari K, Rahimi N, Kazlauskas A (1999) Hepatocyte growth factor receptor in human RPE cells: implications in proliferative vitreoretinopathy. Invest Ophthalmol Vis Sci 40: 149–156

    CAS  PubMed  Google Scholar 

  20. Machemer R (1977) Massive periretinal proliferation: a logical approach to therapy. Trans Am Ophthalmol Soc 75: 556–586

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  22. Mandelcorn M, Machemer R, Fineberg E (1975) Proliferation and metaplasia of intravitreal retinal pigment epithelium cell autotransplant. Am J Ophthalmol 80: 227–237

    CAS  PubMed  Google Scholar 

  23. Mazure A, Grierson I (1992) In vitro studies of the contractility of cell types involved in proliferative vitreoretinopathy. Invest Ophthlamol Vis Sci 33: 3407–3416

    CAS  Google Scholar 

  24. Mueller-Jensen K, Machemer R, Azarnia R (1975) Autotransplantation of retinal pigment epithelium in intravitreal diffusion chamber. Am J Ophthalmol 80: 530–537

    CAS  PubMed  Google Scholar 

  25. Newsome D, Rodrigues M, Machemer R (1981) Human massive periretinal proliferation. In vitro characteristics of cellular components. Arch Ophthalmol 99: 873–880

    CAS  PubMed  Google Scholar 

  26. Pena RA, Jerdan JA, Glaser BM (1994) Effects of TGF-ß and TGF-ß neutralizing antibodies on fibroblast-induced collagen gel contraction: Implications for proliferative vitreoretinopathy. Invest Ophthalmol Vis Sci 35: 2804–2808

    CAS  PubMed  Google Scholar 

  27. Radtke N, Tano Y, Chandler D, Machemer R (1981) Simulation of massive periretinal proliferation by autotransplantation of retinal pigment epithelial cells in rabbits. Am J Ophthalmol 91: 76–87

    CAS  PubMed  Google Scholar 

  28. Raymond M, Thompson JT (1990) RPE-mediated collagen gel contraction. Inhibition by colchicine and stimulation by TGF-beta. Invest Ophthalmol Vis Sci 31: 1079–1086

    CAS  PubMed  Google Scholar 

  29. Sakamoto T, Hinton DR, Sakamoto H et al. (1994) Collagen gel contraction induced by retinal pigment epithelial cells and choroidal fibroblasts involves the protein kinase c pathway. Curr Eye Res 13: 451–459

    Article  CAS  PubMed  Google Scholar 

  30. Schiro JA, Chan BM, Roswit WT et al. (1991) Integrin alpha 2 beta 1 (VLA-2) mediates reorganization and contraction of collagen matrices by human cells. Cell 67: 403–410

    Article  CAS  PubMed  Google Scholar 

  31. Vinores S, Campochiaro P, Conway B (1990) Ultrastructural and electronimmuno-cytocytochemical characterization of cells in epiretinal membranes. Invest Ophthalmol Vis Sci 31: 14–28

    CAS  PubMed  Google Scholar 

  32. Webster L, Chignell AH, Limb GA (1999) Predominance of MMP-1 and MMP-2 in epiretinal and subretinal membranes of proliferative vitreoretinopathy. Exp Eye Res 68: 91–98

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

Download references

Interessenkonflikt

Der korrespondierende Autor gibt an, dass kein Interessenkonflikt besteht.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to S. Grisanti.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Beutel, J., Lüke, M., Bartz-Schmidt, KU. et al. Vitreal induzierte RPE-Zell-Traktion. Ophthalmologe 106, 893–898 (2009). https://doi.org/10.1007/s00347-008-1847-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00347-008-1847-3

Schlüsselwörter

Keywords

Navigation