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Published on: November 25, 2016
MMP expression in leaking filtering blebs and tears after glaucoma filtering surgery
Nurit Mathalone1, Sylvia Marmor, Michal A Rahat
1Department of Ophthalmology, Carmel Medical Center, Haifa, 34362, Israel. matnurit@yahoo.com
Objective:
Glaucoma filtering surgery may be compromised by cystic blebs which develop more frequently when anti-metabolites are used to arrest wound healing. Matrix metalloproteinases (MMPs) and the naturally occurring tissue inhibitors of metalloproteinases (TIMPs) are essential in connective tissue remodeling and wound healing. This study aimed to determine whether filtering blebs display increased expression of MMP-2, MMP-9, TIMP-1 and TIMP-2, and whether it is reflected in tear fluid.
Methods:
Tissue samples from leaking blebs (n = 5) and control conjunctiva (n = 5) were evaluated by immunohistochemistry for MMP-2, MMP-9, TIMP-1 and TIMP-2. Tear fluid was collected from 12 patients (12 eyes) with cystic blebs and ten patients (ten eyes) with flat blebs following trabeculectomy with Mitomycin C applied and 16 controls. MMP levels were evaluated by zymography and TIMP levels by Western blot analysis.
Results:
Conjunctival tissue was obtained from five eyes with cystic leaking blebs and five control eyes undergoing cataract surgery. More extensive MMP-2 and MMP-9 expression was found in the epithelial and stromal layers of blebs than in control conjunctiva. TIMP-1and TIMP-2 were expressed in all layers of the blebs, but only in the epithelium of control conjunctiva. MMP-2 and proMMP-2 activity in tears from eyes with flat blebs was significantly higher than that of controls, while activity in tears of eyes with cystic blebs was significantly higher than in those with flat blebs. There was no difference in MMP-9 activity between tears of control and post-filtering surgery eyes.
Conclusions:
Increased MMPs and TIMPs expression is associated with the formation of filtering blebs, suggesting involvement of MMPs in bleb remodeling. MMP-2 and ProMMP-2 levels in tear fluid may be markers for bleb configuration.
Insights
Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are involved in filtering bleb formation after glaucoma surgery. MMP-2 and ProMMP-2 tear levels may indicate bleb characteristics.
Area of Science:
- Ophthalmology
- Wound Healing Biology
Background:
- Glaucoma filtering surgery can be complicated by cystic blebs, particularly when anti-metabolites are used.
- Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) play crucial roles in tissue remodeling and wound healing.
Purpose of the Study:
- To investigate the expression of MMP-2, MMP-9, TIMP-1, and TIMP-2 in filtering blebs.
- To determine if MMP and TIMP levels in tear fluid correlate with bleb morphology.
Main Methods:
- Immunohistochemistry was used to analyze MMP and TIMP expression in conjunctival tissue samples from blebs and controls.
- Zymography and Western blot analysis were performed on tear fluid samples to quantify MMP and TIMP levels.
Main Results:
- Filtering blebs showed increased expression of MMP-2 and MMP-9 in epithelial and stromal layers compared to controls.
- TIMP-1 and TIMP-2 were found in all layers of blebs but only in the epithelium of control conjunctiva.
- Tear fluid analysis revealed significantly higher MMP-2 and proMMP-2 activity in eyes with flat and cystic blebs compared to controls, with the highest levels in cystic blebs.
Conclusions:
- Elevated MMP and TIMP expression is associated with filtering bleb formation, indicating their role in bleb remodeling.
- MMP-2 and ProMMP-2 levels in tear fluid may serve as potential biomarkers for predicting bleb configuration after glaucoma surgery.
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