Abstract
Purpose::
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.
Methods::
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.
Results::
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.
Conclusions::
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.
Keywords: conjunctiva • microscopy: electron microscopy • pathobiology