Effect of latanoprost and timolol on the histopathology of the rabbit conjunctiva.
OBJECTIVE
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 blebs.
Mietz
H
H
Department of Ophthalmology, University of Cologne, 50924 Koeln, Germany. h.mietz@uni-koeln. de
Schlötzer-Schrehardt
U
U
Strassfeld
C
C
Krieglstein
G K
GK
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D003094:Collagen / Q000378:metabolism; D003228:Conjunctiva / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D004338:Drug Combinations; D005109:Extracellular Matrix / Q000187:drug effects; D005260:Female; D007124:Immunoenzyme Techniques; D007429:Intraocular Pressure / Q000187:drug effects; D000077338:Latanoprost; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D011461:Prostaglandins F, Synthetic / Q000494:pharmacology*; D011817:Rabbits; D013999:Timolol / Q000494:pharmacology*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D015854:Up-Regulation
D000959:Antihypertensive Agents; D004338:Drug Combinations; D011461:Prostaglandins F, Synthetic; D019716:Tissue Inhibitor of Metalloproteinase-2; D000077338:Latanoprost; D013999:Timolol; D003094:Collagen; D019278:Matrix Metalloproteinase 3