Abstract
Background
We investigated the activity of matrix metalloproteinase (MMP)−2 and −9 and the protein levels of MMP−1, −3, −8 and the tissue inhibitor of MMPs (TIMP)−1 in the subretinal fluid (SRF) of patients with rhegmatogenous retinal detachment (RRD) and establishment of potential correlations with clinical parameters.
Methods
Thirty-seven SRF from RRD patients and nine vitreous samples from the human eye of organ donors (controls) were collected and assayed for MMP−1,−3,−8 and TIMP−1 levels using ELISA and for MMP−2 and −9 activity employing gelatin zymography.
Results
MMP−1, MMP−3, MMP−8, proMMP−2, proMMP−9, MMP−9 and TIMP−1 levels were higher in SRF compared with vitreous fluid. Overall, MMPs and TIMPs were differentially expressed in SRF with respect to duration and extent of RRD, as well as to stage of proliferative vitreoretinopathy. Regression analysis for all data indicated that a model consisting of MMP−3, MMP−8 and proMMP−9 could estimate the extent of RRD.
Conclusions
MMPs and TIMP−1 levels are elevated in SRF during RRD. A regression model consisting of MMP−3, MMP−8 and proMMP−9 may be proved to be of potential use in providing information for evaluation of the extent of RRD.
Similar content being viewed by others
References
Abu El-Asrar AM, Dralands L, Veckeneer M, Geboes K, Missottn L, Van Aelst I, Opdenakker G (1998) Gelatinase B in proliferative vitreoretinal disorders. Am J Ophthalmol 125:844–851
Alexander JP, Bradley JMB, Gabourel JD, Acott TS (1990) Expression of matrix metalloproteinases and inhibitors by human retinal pigment epithelium. Invest Ophthalmol Vis Sci 31:2520–2528
Armstrong PW, Moe GW, Howard RJ, Grima EA, Cruz TF (1994) Structural remodelling in heart failure: gelatinase induction. Can J Cardiol 10:214–220
Aylward GW (2004) Proliferative vitreoretinopathy. In: Yanoff D, Duker JS (eds) Ophthalmology. Mosby, St Louis, pp 1002–1006
Bachmeier BE, Nerlich AG, Boukamp P, Lichtinghagen R, Tschesche H, Fritz H, Fink E (2000) Human keratinocyte cell lines differ in the expression of the collagenolytic matrix metalloproteinases −1, −8 and −13 and of TIMP−1. Biol Chem 381:509–516
Behzadian MA, Wang XL, Windsor LJ, Ghaly N, Caldwell RB (2001) TGF-β increases retinal endothelial cell permeability by increasing MMP−9: possible role of glial cells in endothelial cells in endothelial barrier function. Invest Ophthalmol Vis Sci 42:853–859
Borden P, Heller RA (1997) Transcriptional control of matrix metalloproteinases and the tissue inhibitors of matrix metalloproteinases. Crit Rev Euk Gene Exp 7:159–178
Brinckerhoff CE (1992) Regulation of metalloproteinase gene expression: implications for osteoarthritis. Crit Rev Euk Gene Exp 2:145–164
Cao J, Sato H, Takino T, Seiki M (1995) The C-terminal region of membrane type matrix metalloproteinase is a functional trans-membrane domain required for pro-gelatinase A activation. J Biol Chem 270:801–805
Chambers AF, Matrisian LM (1997) Changing views of the role of matrix metalloproteinases in metastasis. J Natl Cancer Inst 89:1260–1270
Eichler W, Friedrichs U, Thies A, Tratz C, Wiedermann P (2002) Modulation of matrix metalloproteinase and TIMP−1 expression by cytokines in human RPE cells. Invest Ophthalmol Vis Sci 43:2767–2773
El Bradey M, Cheng L, Bartsch DU, Appelt K, Rodanant N, Bergeron-Lynn G, Freeman WR (2004) Preventive versus treatment effect of AG3340, a potent matrix metalloproteinase inhibitor in a rat model of choroidal neovascularization. J Ocul Pharmacol Ther 20:217–236
Gomez DE, Alonso DF, Yoshiji H, Thorgeirsson UP (1997) Tissue inhibitors of metalloproteinases: structure, regulation and biological functions. Eur J Cell Biol 74:111–122
Gonzalez-Avila G, Mendez D, Lozano D, Ramos C, Delgado J, Iturria C (2004) Role of retinal detachment subretinal fluid on extracellular matrix metabolism. Ophthalmologica 218:49–56
Hunt RC, Fox A, al Pakalnis V, Sigel MM, Kosnosky W, Choudhury P, Black EP, (1993) Cytokines cause cultured retinal pigment epithelial cells to secrete metalloproteinases and to contract collagen gels. Invest Ophthalmol Vis Sci 34:3179–3186
Itoh Y, Binner S, Nagase H (1995) Steps involved in activation of the complex of promatrix metalloproteinase 2 (progelatinase A) and tissue inhibitor of metalloproteinases (TIMP)−2 by 4-aminophenylmercuric acetate. Biochem J 308:645–651
Karakiulakis G, Papanikolaou C, Jankovic SM, Aletras A, Papakonstantinou E, Vretou E, Mirtsou-Fidani V (1997) Increased type IV collagen-degrading activity in metastases originating from primary tumors of the human colon. Invasion Metastasis 17:158–168
Kon CH, Occleston NL, Charteris D, Daniels J, Ayward GW, Khaw PT (1998) A prospective study of matrix metalloproteinases in proliferative vitreoretinopathy. Invest Ophthalmol Vis Sci 39:1524–1529
Leu ST, Batni S, Radeke MJ, Johnson LV, Anderson DH, Clegg DO (2002) Drusen are cold spots for proteolysis: expression of matrix metalloproteinases and their tissue inhibitor proteins in age-related macular degeneration. Exp Eye Res 74:141–154
Majka S, McGuire P, Colombo S, Das A (2001) The balance between proteinases and inhibitors in a murine model of proliferative retinopathy. Invest Ophthalmol Vis Sci 42:210–215
Matsubara M, Girard MT, Kublin CL, Cintron C, Fini ME (1991) Differential roles for two gelatinolytic enzymes of the matrix metalloproteinase family in the remodelling cornea. Dev Biol 147:425–439
Meller D, Li DQ, Tseng SC (2000) Regulation of collagenase, stromelysin and gelatinase B in human conjuctival and conjuctivochalasis fibroblasts by interleukin-1beta and tumor necrosis factor-alpha. Invest Ophthalmol Vis Sci 41:2922–2929
Papakonstantinou E, Dionyssopoulos A, Aletras AJ, Pesintzaki C, Minas A, Karakiulakis G (2004) Expression of matrix metalloproteinases and their endogenous tissue inhibitors in skin lesions from patients with tuberous sclerosis. J Am Acad Dermatol 51:526–533
Plantner JJ, Jiang C, Smine A (1998) Increase in interphotoreceptor matrix gelatinase A (MMP−2) associated with age-related macular degeneration. Exp Eye Res 67:637–645
Retina Society Terminology Committee (1983) The classification of retinal detachment with proliferative vitreoretinopathy. Am J Ophthalmol 90:121–125
Salzmann J, Limb GA, Khaw PT, Gregor ZJ, Webster L, Chignell AH, Charteris DG (2000) Matrix metalloproteinases and their natural inhibitors in fibrovascular membranes of proliferative diabetic retinopathy. Br J Ophthalmol 84:1091–1096
Sethi CS, Bailey TA, Luthert PJ, Chong NH (2000) Matrix metalloproteinase biology applied to vitreoretinal disorders. Br J Ophthalmol 84:654–666
Sheridan CM, Occleston NL, Hiscott P, Kon CH, Khaw PT, Grierson I (2001) Matrix metalloproteinases: a role in the contraction of vitreo-retinal scar tissue. Am J Pathol 159:1555–1566
Sivak JM, Fini E (2002) MMPs in the eye: emerging roles for matrix metallo-proteinases in ocular pathology. Prog Retin Eye Res 21:1–14
Skiles JW, Gonella NC, Jeng AY (2001) The design, structure and therapeutic application of matrix metalloproteinase inhibitors. Curr Med Chem 8:425–474
Sternlicht MD, Werb Z (2001) How matrix metalloproteinases regulate cell behavior. Annu Rev Cell Dev Biol 17:463–516
Stetler-Stevenson WG, Aznavoorian S, Liotta LA (1993) Tumor cell interactions with the extracellular matrix during invasion and metastasis. Annu Rev Cell Biol 9:541–573
Visse R, Nagase H (2003) Matrix metalloproteinases and tissue inhibitors of metalloproteinases-structure, function, and biochemistry. Circ Res 92:827–839
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
Wilkinson CP (2004) Rhegmatogenous retinal detachment. In: Yanoff D, Duker JS (eds) Ophthalmology. Mosby, St Louis, pp 982–989
Wong TTL, Sethi C, Daniels JT, Limb GA, Murphy G, Khaw PT (2002) Matrix metalloproteinases in disease and repair processes in the anterior segment. Surv Ophthalmol 47:239–256
Zhang X, Sakamoto T, Hata Y, Kubota T, Hisatomi T, Murata T, Ishibashi T, Inomata H (2002) Expression of matrix metalloproteinases and their inhibitors in experimental retinal ischemia-perfusion injury in rats. Exp Eye Res 74:577–584
Acknowledgements
CS and SAD were supported by ”Heraklitos” grant, EPEAEK II, Ministry of Education of Greece; funded by the 3rd Community Support Framework of the European Union.z
Author information
Authors and Affiliations
Corresponding author
Additional information
The last two authors share senior authorship.
Rights and permissions
About this article
Cite this article
Symeonidis, C., Diza, E., Papakonstantinou, E. et al. Expression of matrix metalloproteinases in the subretinal fluid correlates with the extent of rhegmatogenous retinal detachment. Graefe's Arch Clin Exp Ophthalmol 245, 560–568 (2007). https://doi.org/10.1007/s00417-006-0386-3
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00417-006-0386-3