Skip to main content
Log in

Proteinases in subretinal fluid

  • Clinical Investigation
  • Published:
Graefe's Archive for Clinical and Experimental Ophthalmology Aims and scope Submit manuscript

Abstract

⊎ Background: Degradation of the extracellular matrix by secreted proteases is connected to cell migration and proliferation in invasive growth and in scar tissue formation. In retinal detachment, retinal pigment epithelium (RPE) cells loosened from their monolayer are often seen in the subretinal fluid (SRF) and the vitreous, where they may participate in the scar tissue formation of proliferative vitreoretinopathy. To evaluate the role of SRF constituents on the release of RPE cells, we analyzed SRF in patients with retinal detachment for the presence of enzymes able to degrade extracellular matrix. ⊎ Methods: SRF was collected altogether from 16 patients undergoing retinal reattachment surgery and analyzed for activities against some of the key enzymes in extracellular proteolysis, namely collagenases, gelatinases, elastase and cathepsin G. ⊎ Results: Seventy-two-kilodalton gelatinase was found in all SRF samples studied, whereas the neurophil-type 92-kDa gelatinase could not be detected. Low collagenase, elastase and cathepsin G activities could also be detected in some samples. ⊎ Conclusions: The predominant type of matrix metalloproteinase present in SRF is the 72-kDa MMP-2. The proteolytic activity in SRF may be connected to the release of RPE cells into SRF and to degradation of components of the vitreous exposed to SRF.

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.

Institutional subscriptions

Similar content being viewed by others

References

  1. Alexander JP, Bradley JM, Gabourel JD, Acott TS (1990) Expression of matrix metalloproteinases and inhibitor by human retinal pigment epithelium. Invest Ophthalmol Vis Sci 31:2520–2528

    Google Scholar 

  2. Bieth J, Spiess B, Wermuth CG (1974) The synthesis and analytical use of a highly sensitive and convenient substrate of elastase. Biochem Med 11:350–357

    Google Scholar 

  3. Brinkedal-Hansen H (1993) Matrix metal loproteinases. J Periodontol 64:477–484

    Google Scholar 

  4. Brown DJ, Hamdi H, Huang ZS, Kenney MC (1994) Vitreous derived metalloproteinase disrupts the vitreous structure. Invest Ophthalmol Vis Sci 35 [Suppl]:1459

    Google Scholar 

  5. Campoichiaro PA, Jerdan JA, Glaser BM (1986) The extracellular matrix of human retinal pigment epithelial cells in vivo and its synthesis in vitro. Invest Ophthalmol Vis Sci 27:1615–1621

    Google Scholar 

  6. Chu P, Grunwald GB (1991) Functional inhibition of retinal pigment epithelial cell-substrate adhesion with a monoclonal antibody against the beta 1 subunit of integrin. Invest Ophthalmol Vis Sci 32:1763–1769

    Google Scholar 

  7. Emonard H, Grimaud JA (1990) Matrix metal loproteases. A review. Cell Mol Biol 36:131–153

    Google Scholar 

  8. Feeney L, Burns RP, Mixon RM (1975) Human subretinal fluid. Arch Ophthalmol 93:62–69

    Google Scholar 

  9. Garbisa S, Ballin M, Daga-Gordini D (1986) Transient expression of type IV collagenolytic metalloproteinase by human mononuclear phagocytes. J Biol Chem 261:2369–2375

    Google Scholar 

  10. Hibbs MS, Hasty KA, Seyer JM, Kang AH, Mainardi CM (1985) Biochemical and immunological characterization of the secreted forms of human neutrophil gelatinase. J Biol Chem 260:2493–2500

    Google Scholar 

  11. Immonen IJR, Salonen E-M, Vaheri AI, Laatikainen LT (1988) Plasmin in subretinal fluid. Acta Ophthalmol 66:647–651

    Google Scholar 

  12. Immonen I, Stephens RW, Salonen EM, Laatikainen L, Sim P-S, Vaheri A (1989) Tissue-type plasminogen activator in subretinal fluid. Curr Eye Res 8:249–252

    Google Scholar 

  13. Kalebic T, Garbisa S, Glaser B, Liotta LA (1983) Basement membrane collagen: degradation by migrating endothelial cells. Science 221:281–283

    Google Scholar 

  14. Keski-Oja J, Lohi J, Tuuttila A, Tryggvarson K, Vartio T (1992) Proteolytic processing of the 72000-Da type IV collagenase by urokinase plasminogen activator. Exp Cell Res 202:471–476

    Google Scholar 

  15. Kivirikko KI, Laitinen O, Prockop DJ (1991) Modifications of a specific assay for hydroxyproline in urine. Anal Biochem 19:249–255

    Google Scholar 

  16. Konttinen YT, Lindy O, Suomalainen K, Ritchlin C, Saari H, Vauhkonen M, Lauhio A, Santavirta S, Sorsa T (1991) Substrate specificity and activation mechanism of collagenase from human rheumatoid synovium. Matrix 11:395–403

    Google Scholar 

  17. Lefebre V, Peeters-Joris C, Vaes G (1991) Production of gelatin-degrading matrix metal loproteinases (“type IV collagenases”) and inhibitors by articular chondrocytes during their differentiation by serial subcultures and under stimulation by interleukin-1 and tumor necrosis factor alpha. Biochim Biophys Acta 1094:8–18

    Google Scholar 

  18. Linsenmayer TF (1991) Collagen. In: Hay E (ed) Cell biology of extracellular matrix. Plenum Press, New York

    Google Scholar 

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

    Google Scholar 

  20. Mainardi CL, Hibbs MS, Hasty KA, Seyer JM (1984) Purification of a type IV collagen degrading metalloprotease from rabbit alveolar macrophages. Collagen Relat Res 4:479–492

    Google Scholar 

  21. Mayne R, Brewton RG, Mayne PM, Baker JR (1993) Isolation and characterization of the chains of type V/type XI collagen present in bovine vitreous. J Biol Chem 268:9381–9386

    Google Scholar 

  22. Miller EJ, Rhodes KR (1982) Preparation and characterization of the different type of collagen. In: Cunningham LW, Fredriksen DW (eds) Structural and contractile proteins, part A. (Methods in enzymology vol LXXXII) Academic Press, New York

    Google Scholar 

  23. Murphy G, Ward R, Hembry RM, Reynolds JJ, Kuhn K, Tryggvarson K (1989) Characterization of gelatinase from pig polymorphonuclear leukocytes. Biochem J 258:463–472

    Google Scholar 

  24. Nakajima MC, Powers JC, Ashe BM, Zimmerman M (1979) Mapping of the extended substrate binding site of cathepsin G and human leukocyte elastase. J Biol Chem 254:4027–4032

    Google Scholar 

  25. Overall CM, Sodek J (1987) Initial chacterization of a neutral metalloproteinase, active on native 3/4-collagen fragments, synthetized by ROS 17/2.8 osteoblastic cells, periodontal fibroblasts, and identified in gingival crevicular fluid. J Dent Res 66:1271–1282

    Google Scholar 

  26. Platner JJ (1992) The presence of neutral metalloproteolytic activity and metalloproteinase inhibitors in the interphotoreceptor matrix. Curr Eye Res 11:91–101

    Google Scholar 

  27. Prockop DJ, Udenfriend S (1960) A specific method for the analysis of hydroxyproline in tissues and urine. Anal Biochem 1:228–239

    Google Scholar 

  28. Quinn TA, Bruner WE, Singerman LJ, Plantner JJ (1994) Matrix metalloproteinases of the interphotoreceptor matrix and vitreous. Invest Ophthalmol Vis Sci 35 [Suppl]:1459

    Google Scholar 

  29. Retina Society Terminology Committee (1983) The classification of retinal detachment with proliferative vitreoretinopathy. Ophthalmology 90:121–125

    Google Scholar 

  30. Salo T, Lyons JG, Rahemtulla F, Birkedal-Hansen H, Larjava H (1991) Transforming growth factor beta1 upregulates type IV collagenase expression in cultured human keratinocytes. J Biol Chem 266:11435–11441

    Google Scholar 

  31. Seery CM, Davison PF (1991) Collagens of the bovine vitreous. Invest Ophthalmol Vis Sci 32:1540–1550

    Google Scholar 

  32. Seltzer JL, Adams SA, Grant GA, Eisen AZ (1981) Purification and properties of a gelatin-specific protease from human skin. J Biol Chem 256:4662–4668

    Google Scholar 

  33. Springman EB, Angleton EL, Birkedal-Hansen H, Van Wart HE (1990) Multiple modes of activation of latent human collagenase: evidence for the role of Cys73 active site zinc complex in latency and a ‘cysteine switch’ mechanism for activation. Proc Natl Acad Sci USA 87:364–368

    Google Scholar 

  34. Turksen K, Opas M, Kalnin VI (1989) Cytoskeleton, adhesion and extracellular matrix of fetal human retinal pigmented epithelial cells in culture. Ophthalmic Res 21:56–66

    Google Scholar 

  35. Turto H, Lindy S, Uitto V-J, Wegelius O, Uitto J (1977) Human leukocyte collagenase: characterization of enzyme kinetics by a new method. Anal Biochem 83:557–569

    Google Scholar 

  36. Wiedemann P, Heimann K (1992) Proliferative vitreoretinopathy. Curr Opin Ophthalmol 3:357–365

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Immonen, I., Konttinen, Y.T., Sorsa, T. et al. Proteinases in subretinal fluid. Graefe's Arch Clin Exp Ophthalmol 234, 105–109 (1996). https://doi.org/10.1007/BF00695249

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00695249

Keywords

Navigation