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Holger Mietz, Ursula Schlötzer–Schrehardt, Carsten Strassfeld, Günter K. Krieglstein; Effect of Latanoprost and Timolol on the Histopathology of the Rabbit Conjunctiva. Invest. Ophthalmol. Vis. Sci. 2001;42(3):679-687.
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purpose. Long-term medical treatment of glaucoma has an effect on the conjunctiva,
possibly affecting the outcome of subsequent filtering surgery. The
type and extent of these tissue changes caused by frequently used
medications is important. An animal study using rabbits was performed
to assess the tissue changes caused by timolol, latanoprost, and a
combination of both substances.
methods. Rabbits were treated with timolol, latanoprost, or a combination of
these drugs for 18 months. Conjunctival specimens were examined by
light microscopy, quantitative transmission electron microscopy, and
immunohistochemistry with antibodies against matrix metalloproteinase
(MMP)-3 and tissue inhibitors of metalloproteinase (TIMP)-2.
results. By electron microscopy, the area of subepithelial collagen was
significantly larger (P < 0.03; Mann–Whitney test) in
timolol-treated eyes (71.6%) than in control (52.7%) and
latanoprost-treated eyes (57.7%). An increase of amorphous material
was present in timolol-treated eyes (25.6% versus 7.6% in the
controls) as well as a smaller area of empty spaces (2.5% versus
39.4% in control eyes). Latanoprost-treated eyes had no significant
increase of empty spaces but showed a marked staining for MMP-3 in the
conjunctiva. This staining was not present in control or
timolol-treated eyes. Morphologically, degenerative changes of
fibrocytes were seen in timolol-treated eyes only.
conclusions. A significant increase of subepithelial collagen density was present in
timolol-treated eyes, whereas this finding was not apparent in
latanoprost-treated eyes. Latanoprost-treated eyes showed an
upregulation of MMP-3, which may be the reason for reduced
extracellular matrix accumulation in such eyes. The morphologic feature
of increased subepithelial collagen density and extracellular matrix
changes may relate to failure of filtering
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