Skip to main content
Top
Published in: BMC Ophthalmology 1/2008

Open Access 01-12-2008 | Research article

Matrix metalloproteinases and their tissue inhibitors after selective laser trabeculoplasty in pseudoexfoliative secondary glaucoma

Authors: Mauro Cellini, Pietro Leonetti, Ernesto Strobbe, Emilio C Campos

Published in: BMC Ophthalmology | Issue 1/2008

Login to get access

Abstract

Background

The aim of this study was to assess changes in metalloproteinases (MMP-2) and tissue inhibitor of metalloproteinases (TIMP-2) following selective laser trabeculoplasty (SLT) in patients with pseudoexfoliative glaucoma (PEXG).

Methods

We enrolled 15 patients with PEXG and cataracts (PEXG-C group) and good intraocular pressure (IOP) controlled with β-blockers and dorzolamide eye drops who were treated by cataract phacoemulsification and 15 patients with pseudoexfoliative glaucoma (PEXG-SLT group). The PEXG-SLT patients underwent a trabeculectomy for uncontrolled IOP in the eye that showed increased IOP despite the maximum drug treatment with β-blockers and dorzolamide eye drops and after ineffective selective laser trabeculoplasty (SLT). The control group consisted of 15 subjects with cataracts. Aqueous humor was aspirated during surgery from patients with PEXG-C, PEXG-SLT and from matched control patients with cataracts during cataract surgery or trabeculectomy. The concentrations of MMP-2 and TIMP-2 in the aqueous humor were assessed with commercially available ELISA kits.

Results

In PEXG-SLT group in the first 10 days after SLT treatment a significant reduction in IOP was observed: 25.8 ± 1.9 vs 18.1.0 ± 1.4 mm/Hg (p < 0.001), but after a mean time of 31.5 ± 7.6 days IOP increased and returned to pretreatment levels: 25.4 ± 1.6 mm/Hg (p < 0.591). Therefore a trabeculectomy was considered necessary.
The MMP-2 in PEXG-C was 57.77 ± 9.25 μg/ml and in PEXG-SLT was 58.52 ± 9.66 μg/ml (p < 0.066). TIMP-2 was 105.19 ± 28.53 μg/ml in PEXG-C and 105.96 ± 27.65 μg/ml in PEXG-SLT (p < 0.202). The MMP-2/TIMP-2 ratio in the normal subjects was 1.11 ± 0.44. This ratio increase to 1.88 ± 0.65 in PEXG-C (p < 0.001) and to 1.87 ± 0.64 in PEXG-SLT (p < 0.001). There was no statistically significant difference between the PEXG-C and PEXG-SLT ratios (p < 0.671).

Conclusion

This case series suggest that IOP elevation after SLT can be a serious adverse event in some PEXG patients. The IOP increase in these cases would be correlated to the failure to decrease the TIMP-2/MMP-2 ratio.

Trial registration

Current Controlled Trials ISRCTN79745214
Literature
1.
go back to reference Weinreb RN, Tsai S: Laser trabeculoplasty. The glaucomas: glaucoma therapy. Edited by: Ritch R, Shields MB, Krupin T. 1996, St Louis: Mosby-Year Book, 1575-90. 2 Weinreb RN, Tsai S: Laser trabeculoplasty. The glaucomas: glaucoma therapy. Edited by: Ritch R, Shields MB, Krupin T. 1996, St Louis: Mosby-Year Book, 1575-90. 2
2.
go back to reference Melamed S, Simon GJB, Levkovitch-Verbin H: Selective laser trabeculoplasty as primary treatment for open-angle glaucoma. Arch Ophthalmol. 2003, 121: 957-960. 10.1001/archopht.121.7.957.CrossRefPubMed Melamed S, Simon GJB, Levkovitch-Verbin H: Selective laser trabeculoplasty as primary treatment for open-angle glaucoma. Arch Ophthalmol. 2003, 121: 957-960. 10.1001/archopht.121.7.957.CrossRefPubMed
3.
go back to reference Wise JB, Witter SL: Argon laser therapy for open angle glaucoma: a pilot study. Arch Ophthalmol. 1979, 97: 319-22.CrossRefPubMed Wise JB, Witter SL: Argon laser therapy for open angle glaucoma: a pilot study. Arch Ophthalmol. 1979, 97: 319-22.CrossRefPubMed
4.
go back to reference Latina MA, Park C: Selective targeting of trabecular meshwork cells: in vitro studies of pulsed and Q-sw laser interactions. Exp Eye Res. 1995, 60: 359-72. 10.1016/S0014-4835(05)80093-4.CrossRefPubMed Latina MA, Park C: Selective targeting of trabecular meshwork cells: in vitro studies of pulsed and Q-sw laser interactions. Exp Eye Res. 1995, 60: 359-72. 10.1016/S0014-4835(05)80093-4.CrossRefPubMed
5.
go back to reference Damji KF, Shah KC, Rock WJ, Bains HS, Hodge WG: Selective laser trabeculoplasty vs argon laser trabeculoplasty: a prospective randomised clinical trial. Br J Ophthalmol. 1999, 83: 718-722.CrossRefPubMedPubMedCentral Damji KF, Shah KC, Rock WJ, Bains HS, Hodge WG: Selective laser trabeculoplasty vs argon laser trabeculoplasty: a prospective randomised clinical trial. Br J Ophthalmol. 1999, 83: 718-722.CrossRefPubMedPubMedCentral
6.
go back to reference Sanfilippo P: A review of argon and selective laser trabeculoplasty as primary treatments of open-angle glaucoma. Clin Exp Optom. 1999, 82 (6): 225-229.CrossRefPubMed Sanfilippo P: A review of argon and selective laser trabeculoplasty as primary treatments of open-angle glaucoma. Clin Exp Optom. 1999, 82 (6): 225-229.CrossRefPubMed
7.
go back to reference Kramer TR, Noecker RJ: Comparison of the morphologic changes after selective laser trabeculoplasty and argon laser trabeculoplasty in human eye bank eyes. Ophthalmology. 2001, 108: 773-779. 10.1016/S0161-6420(00)00660-6.CrossRefPubMed Kramer TR, Noecker RJ: Comparison of the morphologic changes after selective laser trabeculoplasty and argon laser trabeculoplasty in human eye bank eyes. Ophthalmology. 2001, 108: 773-779. 10.1016/S0161-6420(00)00660-6.CrossRefPubMed
8.
go back to reference Bradly JM, Anderssohn AM, Colvis CM, Parshley DE, Zhu XH, Ruddat MS, Samples JR, Acott TS: Mediation of laser trabeculoplasty induced matrix metalloproteinase expression by IL-1β and TNFα. Invest Ophthalmol Vis Sci. 2000, 41: 422-430. Bradly JM, Anderssohn AM, Colvis CM, Parshley DE, Zhu XH, Ruddat MS, Samples JR, Acott TS: Mediation of laser trabeculoplasty induced matrix metalloproteinase expression by IL-1β and TNFα. Invest Ophthalmol Vis Sci. 2000, 41: 422-430.
9.
go back to reference Latina MA, DeLeon JM: Selective laser trabeculoplasty. Ophthalmol Clin N Am. 2005, 18: 409-419. 10.1016/j.ohc.2005.05.005.CrossRef Latina MA, DeLeon JM: Selective laser trabeculoplasty. Ophthalmol Clin N Am. 2005, 18: 409-419. 10.1016/j.ohc.2005.05.005.CrossRef
10.
go back to reference Latina MA, Tumbocon JA: Selective laser trabeculoplasty a new treatment option for open angle glaucoma. Curr Opin Ophthalmol. 2002, 13: 94-96. 10.1097/00055735-200204000-00007.CrossRefPubMed Latina MA, Tumbocon JA: Selective laser trabeculoplasty a new treatment option for open angle glaucoma. Curr Opin Ophthalmol. 2002, 13: 94-96. 10.1097/00055735-200204000-00007.CrossRefPubMed
11.
go back to reference Harasymowycz PJ, Papamatheakis DG, Latina M, De Leon M, Lesk M, Damji KF: Selective laser trabeculoplasty (SLT) complicated by intraocular pressure elevation in eyes with heavily pigmented trabecular meshworks. Am J Ophthalmol. 2005, 139: 1110-1113. 10.1016/j.ajo.2004.11.038.CrossRefPubMed Harasymowycz PJ, Papamatheakis DG, Latina M, De Leon M, Lesk M, Damji KF: Selective laser trabeculoplasty (SLT) complicated by intraocular pressure elevation in eyes with heavily pigmented trabecular meshworks. Am J Ophthalmol. 2005, 139: 1110-1113. 10.1016/j.ajo.2004.11.038.CrossRefPubMed
12.
go back to reference Parshley DE, Bradley JM, Fisk A, Hadaegh A, Samples JR, Van Buskirk EM, Acott TS: Laser trabeculoplasty induces stromelysin expression by trabecular juxtacanilicular cells. Invest Ophthalmol Vis Sci. 1996, 37: 795-804.PubMed Parshley DE, Bradley JM, Fisk A, Hadaegh A, Samples JR, Van Buskirk EM, Acott TS: Laser trabeculoplasty induces stromelysin expression by trabecular juxtacanilicular cells. Invest Ophthalmol Vis Sci. 1996, 37: 795-804.PubMed
14.
go back to reference Springman EB, Angleton EL, Birkedal-Hansen H, Van Wart HE: Multiple modes of activation of latent human fibroblast collagenases: evidence for the role of a Cys37 active-site zinc complex in latency and a "cysteine switch" mechanism for activation. Proc Nat Acad Sci USA. 1990, 87: 364-368. 10.1073/pnas.87.1.364.CrossRefPubMedPubMedCentral Springman EB, Angleton EL, Birkedal-Hansen H, Van Wart HE: Multiple modes of activation of latent human fibroblast collagenases: evidence for the role of a Cys37 active-site zinc complex in latency and a "cysteine switch" mechanism for activation. Proc Nat Acad Sci USA. 1990, 87: 364-368. 10.1073/pnas.87.1.364.CrossRefPubMedPubMedCentral
15.
go back to reference Murphy G, Willenbrock F, Crabbe T, O'Shea M, Ward R, Atkinson S, O'Connell J, Docherty A: Regulation of matrix metalloproteinase activity. Ann NY Acad Sci. 1994, 732: 31-41. 10.1111/j.1749-6632.1994.tb24722.x.CrossRefPubMed Murphy G, Willenbrock F, Crabbe T, O'Shea M, Ward R, Atkinson S, O'Connell J, Docherty A: Regulation of matrix metalloproteinase activity. Ann NY Acad Sci. 1994, 732: 31-41. 10.1111/j.1749-6632.1994.tb24722.x.CrossRefPubMed
16.
go back to reference Nagase H, Enghild JJ, Suzuki K, Salvesen G: Stepwise activation mechanisms of the precursor of matrix metalloproteinase 3 (stromelysin) by proteinases and (4-aminophenyl) mercuric acetate. Biochemistry. 1990, 29: 5783-5789. 10.1021/bi00476a020.CrossRefPubMed Nagase H, Enghild JJ, Suzuki K, Salvesen G: Stepwise activation mechanisms of the precursor of matrix metalloproteinase 3 (stromelysin) by proteinases and (4-aminophenyl) mercuric acetate. Biochemistry. 1990, 29: 5783-5789. 10.1021/bi00476a020.CrossRefPubMed
17.
go back to reference Ogata Y, Enghild JJ, Nagase H: Matrix metalloproteinase 3 (stromelysin) activates the precursor for the human matrix metalloproteinase 9. J Biol Chem. 1992, 267: 3581-3584.PubMed Ogata Y, Enghild JJ, Nagase H: Matrix metalloproteinase 3 (stromelysin) activates the precursor for the human matrix metalloproteinase 9. J Biol Chem. 1992, 267: 3581-3584.PubMed
18.
go back to reference Birkedal-Hansen H, Moore WG, Bodden MK, Windosor LJ, Birkedal-Hansen B, De Carlo A, Engler JA: Matrix metalloproteinases: a review. Crit Rev Oral Biol Med. 1993, 4: 197-250.PubMed Birkedal-Hansen H, Moore WG, Bodden MK, Windosor LJ, Birkedal-Hansen B, De Carlo A, Engler JA: Matrix metalloproteinases: a review. Crit Rev Oral Biol Med. 1993, 4: 197-250.PubMed
19.
go back to reference Denhardt DT, Feng B, Edwards DR, Cocuzzi ET, Malyankar UM: Tissue inhibitor of metalloproteinases (TIMP, aka EPA): structure, control of expression and biological functions. Pharmacol Ther. 1993, 59: 329-341. 10.1016/0163-7258(93)90074-N.CrossRefPubMed Denhardt DT, Feng B, Edwards DR, Cocuzzi ET, Malyankar UM: Tissue inhibitor of metalloproteinases (TIMP, aka EPA): structure, control of expression and biological functions. Pharmacol Ther. 1993, 59: 329-341. 10.1016/0163-7258(93)90074-N.CrossRefPubMed
20.
go back to reference Gomez DE, Alonso DF, Yoshiji H, Thorgeirsson UP: Tissue inhibitor of metalloproteinases: structure regulation and biological functions. Eur J Cell Biol. 1997, 74: 111-122.PubMed Gomez DE, Alonso DF, Yoshiji H, Thorgeirsson UP: Tissue inhibitor of metalloproteinases: structure regulation and biological functions. Eur J Cell Biol. 1997, 74: 111-122.PubMed
21.
go back to reference Howard EW, Banda MJ: Binding of tissue inhibitor of metalloproteinases 2 to two distinct sites on human 72-kDa gelatinase. J Biol Chem. 1991, 266: 17972-17977.PubMed Howard EW, Banda MJ: Binding of tissue inhibitor of metalloproteinases 2 to two distinct sites on human 72-kDa gelatinase. J Biol Chem. 1991, 266: 17972-17977.PubMed
22.
go back to reference Schlötzer-Schrehardt U, Lommatzsch J, Kuchle M, Konstas AG, Naumann GO: Matrix metalloproteinases and their inhibitors in acqueous humor of patients with pseudoexfoliation syndrome/glaucoma and primary open-angle glaucoma. Invest Ophthalmol Vis Sci. 2003, 44: 1117-1125. 10.1167/iovs.02-0365.CrossRefPubMed Schlötzer-Schrehardt U, Lommatzsch J, Kuchle M, Konstas AG, Naumann GO: Matrix metalloproteinases and their inhibitors in acqueous humor of patients with pseudoexfoliation syndrome/glaucoma and primary open-angle glaucoma. Invest Ophthalmol Vis Sci. 2003, 44: 1117-1125. 10.1167/iovs.02-0365.CrossRefPubMed
23.
go back to reference Määttä M, Tervahartiala T, Harju M, Airaksinen J, Auto-Harmainen H, Sorsa T: Matrix metalloproteinases and their tussue inhibitors an aqueous humor of patients with primary open angle glaucoma, exfoliation syndrome and exfoliation glaucoma. J Glaucoma. 2005, 14: 64-69. 10.1097/01.ijg.0000145812.39224.0a.CrossRefPubMed Määttä M, Tervahartiala T, Harju M, Airaksinen J, Auto-Harmainen H, Sorsa T: Matrix metalloproteinases and their tussue inhibitors an aqueous humor of patients with primary open angle glaucoma, exfoliation syndrome and exfoliation glaucoma. J Glaucoma. 2005, 14: 64-69. 10.1097/01.ijg.0000145812.39224.0a.CrossRefPubMed
24.
go back to reference Ritch R, Schlötzer-Schrehardt U: Exfoliation Syndrome. Survey Ophthalmol. 2001, 45: 265-314. 10.1016/S0039-6257(00)00196-X.CrossRef Ritch R, Schlötzer-Schrehardt U: Exfoliation Syndrome. Survey Ophthalmol. 2001, 45: 265-314. 10.1016/S0039-6257(00)00196-X.CrossRef
25.
go back to reference Schlötzer-Schrehardt U, Koca MR, Naumann GO, Volkholz H: Pseudoexfoliation syndrome: ocular manifestation of a systemic disorder?. Arch Ophthalmol. 1992, 110: 1752-1756.CrossRefPubMed Schlötzer-Schrehardt U, Koca MR, Naumann GO, Volkholz H: Pseudoexfoliation syndrome: ocular manifestation of a systemic disorder?. Arch Ophthalmol. 1992, 110: 1752-1756.CrossRefPubMed
26.
go back to reference Streeten BW, Li Z-Y, Wallace RN, Eagle RC, Keshgegian AA: Pseudoextoliative fibrillopathy in visceral organs of a patient with pseudoexfoliation syndrome. Arch Ophthalmol. 1992, 110: 1757-1762.CrossRefPubMed Streeten BW, Li Z-Y, Wallace RN, Eagle RC, Keshgegian AA: Pseudoextoliative fibrillopathy in visceral organs of a patient with pseudoexfoliation syndrome. Arch Ophthalmol. 1992, 110: 1757-1762.CrossRefPubMed
27.
go back to reference Carpel EF: Pupillary dilatation in eyes with pseudoexfoliation syndrome. Am J Ophthalmol. 1988, 105: 692-694.CrossRefPubMed Carpel EF: Pupillary dilatation in eyes with pseudoexfoliation syndrome. Am J Ophthalmol. 1988, 105: 692-694.CrossRefPubMed
28.
go back to reference Watson NJ, Winder S, Green FD: Pupil dilatation in the pseudoexfoliation syndrome. Eye. 1995, 9: 341-343.CrossRefPubMed Watson NJ, Winder S, Green FD: Pupil dilatation in the pseudoexfoliation syndrome. Eye. 1995, 9: 341-343.CrossRefPubMed
29.
go back to reference Hansen E, Sellevold OJ: Pseudoexfoliation of the lens capsule, II. Development of the exfoliation syndrome. Acta Ophthalmol (Copenh). 1969, 47 (1): 161-173.CrossRef Hansen E, Sellevold OJ: Pseudoexfoliation of the lens capsule, II. Development of the exfoliation syndrome. Acta Ophthalmol (Copenh). 1969, 47 (1): 161-173.CrossRef
30.
go back to reference Prince AM, Ritch R: Clinical signs of the pseudoexfoliation syndrome. Ophthalmology. 1986, 93: 803-807.CrossRefPubMed Prince AM, Ritch R: Clinical signs of the pseudoexfoliation syndrome. Ophthalmology. 1986, 93: 803-807.CrossRefPubMed
31.
go back to reference Repo LP, Teràsvirta ME, Tuovinen EJ: Generalized peripheral iris transluminance in the pseudoexfoliation syndrome. Ophthalmology. 1990, 97: 1027-1029.CrossRefPubMed Repo LP, Teràsvirta ME, Tuovinen EJ: Generalized peripheral iris transluminance in the pseudoexfoliation syndrome. Ophthalmology. 1990, 97: 1027-1029.CrossRefPubMed
32.
go back to reference Asano A, Schlötzer-Schrehardt U, Naumann GO: A histopathologic study of iris changes in pseudoexfoliation syndrome. Ophthalmology. 1995, 102: 1279-1290.CrossRefPubMed Asano A, Schlötzer-Schrehardt U, Naumann GO: A histopathologic study of iris changes in pseudoexfoliation syndrome. Ophthalmology. 1995, 102: 1279-1290.CrossRefPubMed
33.
go back to reference Konstas AGP, Marshall GE, Cameron SA, Lee WR: Morphology of iris vasculopathy in exfoliation glaucoma. Acta Ophthalmol (Copenh). 1993, 71 (6): 751-759.CrossRef Konstas AGP, Marshall GE, Cameron SA, Lee WR: Morphology of iris vasculopathy in exfoliation glaucoma. Acta Ophthalmol (Copenh). 1993, 71 (6): 751-759.CrossRef
34.
go back to reference Brooks AMV, Gillies WE: Fluorescein angiography and fluorophotometry of the iris in pseudoexfoliation of the lens capsule. Br J Ophthalmol. 1983, 67: 249-254. 10.1136/bjo.67.4.249.CrossRefPubMedPubMedCentral Brooks AMV, Gillies WE: Fluorescein angiography and fluorophotometry of the iris in pseudoexfoliation of the lens capsule. Br J Ophthalmol. 1983, 67: 249-254. 10.1136/bjo.67.4.249.CrossRefPubMedPubMedCentral
35.
go back to reference Vannas A: Vascular changes in pseudoexfoliation of the lens capsule and capsular glaucoma: a fluorescein angiographic and electron microscopic study. Graefes Arch Clin Exp Ophthalmol. 1972, 184: 248-253. 10.1007/BF00413298.CrossRef Vannas A: Vascular changes in pseudoexfoliation of the lens capsule and capsular glaucoma: a fluorescein angiographic and electron microscopic study. Graefes Arch Clin Exp Ophthalmol. 1972, 184: 248-253. 10.1007/BF00413298.CrossRef
36.
go back to reference Hammer T, Schlötzer-Schrehardt U, Naumann GO: Unilateral or asymmetric pseudoexfoliation syndrome?. Arch Ophthalmol. 2001, 119: 1023-1031.CrossRefPubMed Hammer T, Schlötzer-Schrehardt U, Naumann GO: Unilateral or asymmetric pseudoexfoliation syndrome?. Arch Ophthalmol. 2001, 119: 1023-1031.CrossRefPubMed
37.
go back to reference Pohjanpelto PE: The fellow eye in unilateral hypertensive pseudoexfoliation. Am J Ophthalmol. 1973, 75: 216-220.CrossRefPubMed Pohjanpelto PE: The fellow eye in unilateral hypertensive pseudoexfoliation. Am J Ophthalmol. 1973, 75: 216-220.CrossRefPubMed
38.
go back to reference Gharagozloo NZ, Baker RH, Brubaker RF: Aqueous dynamics in exfoliation syndrome. Am J Ophthalmol. 1992, 114: 473-478.CrossRefPubMed Gharagozloo NZ, Baker RH, Brubaker RF: Aqueous dynamics in exfoliation syndrome. Am J Ophthalmol. 1992, 114: 473-478.CrossRefPubMed
39.
go back to reference Jung S, Zhang W, Van Nostrand WE: Pathogenic A beta induces the expression and activation of matrix metalloproteinase-2 in human cerebrovascolar smooth muscle cells. J Neurochem. 2003, 85: 1208-1215. 10.1046/j.1471-4159.2003.01745.x.CrossRefPubMed Jung S, Zhang W, Van Nostrand WE: Pathogenic A beta induces the expression and activation of matrix metalloproteinase-2 in human cerebrovascolar smooth muscle cells. J Neurochem. 2003, 85: 1208-1215. 10.1046/j.1471-4159.2003.01745.x.CrossRefPubMed
Metadata
Title
Matrix metalloproteinases and their tissue inhibitors after selective laser trabeculoplasty in pseudoexfoliative secondary glaucoma
Authors
Mauro Cellini
Pietro Leonetti
Ernesto Strobbe
Emilio C Campos
Publication date
01-12-2008
Publisher
BioMed Central
Published in
BMC Ophthalmology / Issue 1/2008
Electronic ISSN: 1471-2415
DOI
https://doi.org/10.1186/1471-2415-8-20

Other articles of this Issue 1/2008

BMC Ophthalmology 1/2008 Go to the issue