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J. Lampel, U. Schlötzer-Schrehardt, A. G. Boehm, C. Rummelt, F. E. Kruse, L. E. Pillunat; Effect of Latanoprost and Timolol on the Histopathology of the Human Conjunctiva. Invest. Ophthalmol. Vis. Sci. 2007;48(13):1550.
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To determine the effect of the anti-glaucoma medications timolol and latanoprost on extracellular matrix organisation and expression of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) in the human conjunctiva.
After informed consent, conjunctival biopsies were obtained at the inferior fornix during routine cataract surgery from 20 patients with primary open-angle glaucoma, who had received a monotherapy either with 0.5% timolol (mean age 75±7 years) or latanoprost (mean age 74±10 years) for 15-21 months and from 10 cataract patients without glaucoma (mean age 76±6 years) serving as controls. Specimens were investigated by light microscopy, quantitative transmission electron microscopy using an automated image-processing system, and immunohistochemistry using antibodies against MMP-1, MMP-3, TIMP-2, TIMP-3, and CD68.
The area occupied by collagen fibers was significantly decreased in latanoprost-treated conjunctival specimens as compared to timolol-treated eyes (31.8% versus 36.6%; p<0.01), but was not significantly different from controls (33.5%). The amount of amorphous material, probably representing proteoglycans, was increased in both treated groups as compared to controls (30.9%; p<0.001), but the difference was less pronounced in latanoprost-treated specimens (38.1%) as compared to timolol-treated eyes (43.3%; p<0.001). Approximately 30-40% of the area measured appeared as optically clear spaces in control eyes, with a significant reduction in both treated groups; this reduction was significantly less in latanoprost-treated specimens (19.0%) compared with timolol-treated eyes (13.4%; p<0.001). A marked upregulation of MMP-1 and MMP-3 protein and moderately increased staining for TIMP-2 and TIMP-3 was found in epithelial cells and subepithelial stromal cells of latanoprost-treated conjunctival tissue, whereas a moderate infiltration with macrophages and inflammatory cells was observed in timolol-treated specimens.
Compared with timolol-treated eyes, latanoprost-treated conjunctival specimens showed a less dense stromal matrix and less pronounced inflammatory infiltration. The upregulation of MMP-1 and MMP-3 in latanoprost-treated eyes might explain the reduction of extracellular matrix accumulation in the conjunctival stroma. Therefore, latanoprost therapy might have a more favorable effect on the outcome of glaucoma filtering surgery.
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