Abstract
Abstract: :
Purpose: Plasminogen Activator Inhibitor 1 (PAI–1) acts as a main regulator of the fibrinolytic system and modulates extracellular matrix proteolysis in an early stage. High concentration of PAI–1 inhibits matrix metalloproteinases (MMP) function by decreasing plasmin and subsequently extracellular matrix degradation which promotes tissue scarring. The overexpression of PAI–1 has been found to correlate with extensive tissue scarring i.e. in the skin, lung and kidney. In the porcine eye, PAI–1 has been found in the ciliary epithelium and aqueous humor and also in the posterior segment of the eye. We investigated the concentration of PAI–1 in the aqueous humor of cataract and glaucoma patients and the correlation with postoperative bleb scarring after trabeculectomy. Methods: In a prospective study, 75 patients, 27 primary open angle glaucoma (POAG), 17 exfoliation (XFS) glaucoma, 7 pigment glaucoma and 24 cataracts were recruited in consecutive series. All glaucoma patients underwent primary trabeculectomy by one surgeon. Intraoperatively sampled aqueous humor (40–180 µl) was analysed for PAI–1 concentration by ELISA (American Diagnostics). Cataract patients served as controls. Standardized masked postoperative bleb scarring was performed and mean follow up was 4.3 months. Results: PAI–1 concentration was significantly increased in exfoliation glaucoma (mean 4.33 +/– 2.65 µg/ml) as compared to cataract patients (mean 2.69 +/– 1.10 µg/ml, P= 0.009) and higher as in POAG patients (mean 3.15 +/– 1.5 µg/ml, P= 0.066) but close to normal level in pigment glaucoma (mean 2.76 +/– 0.72 µg/ml). Concerning postoperative bleb scarring in POAG we found higher concentrations of PAI–1 in the eyes with scarred blebs (n=13, mean 3.58 +/– 1.89 µl) as compared to favourable looking blebs (n=14, mean 2.76 +/–0.96 µl, P=0.162). In exfoliation glaucoma, this difference was even nearly statistically significant (scarred blebs: n=7, mean 5.78 +/–3.66 µl, favourable looking blebs: n=10, mean 3.32 +/–0.89 µl, P= 0.057 student t–test) Conclusions: PAI–1 concentration in the human aqueous humor is elevated in POAG and nearly statistically significant in XFS glaucoma as compared to cataract patients. We found an increased scarring risk of the bleb after trabeculectomy in patients with higher PAI–1 concentrations particulary in XFS glaucoma, where PAI–1 could be used as a prognostic marker for postoperative bleb scarring.
Keywords: wound healing • aqueous • extracellular matrix