Effect of latanoprost and timolol on the histopathology of the rabbit conjunctiva

PURPOSE. Long-term medical treatment of glaucoma has an effect on the conju nctiva, possibly affecting the outcome of subsequent filtering surgery. The type and extent of these tissue changes caused by frequently used medicati ons is important. An animal study using rabbits' was performed to assess th e tissue changes caused by timolol, latanoprost, and a combination of both substances. METHODS. Rabbits were treated with timolol, latanoprost, or a combination o f these drugs for 18 months. Conjunctival specimens were examined by light microscopy, quantitative transmission electron microscopy, and immunohistoc hemistry with antibodies against matrix metalloproteinase (MMP)-3 and tissu e inhibitors of metalloproteinase (TIMP)-2. RESULTS. By electron microscopy, the area of subepithelial collagen was sig nificantly larger (P < 0.03; Mann-Whitney test) in timolol-treated eyes (71 .6%) than in control (52.7%) and latanoprost-treated eyes (57.70%). An incr ease of amorphous material was present in timolol-treated eyes (25.6% versu s 7.6% in the controls) as well as a smaller area of empty spaces (2.5% ver sus 39.4% in control eyes). Latanoprost-treated eyes had no significant inc rease of empty spaces but showed a marked staining for MMP-3 in the conjunc tiva. This staining was not present in control or timolol-treated eyes. Mor phologically, degenerative changes of fibrocytes mere seen in timolol-treat ed eyes only. CONCLUSIONS. A significant increase of subepithelial collagen density was p resent in timolol-treated eyes, whereas this finding was not apparent in la tanoprost-treated eyes. Latanoprost-treated eyes showed an upregulation of MMP-3, which may be the reason for reduced extracellular matrix accumulatio n in such eyes. The morphologic feature of increased subepithelial collagen density and extracellular matrix changes may relate to failure of filterin g blebs.