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H. Mietz, G. Welsandt, C. Jonescu–Cuypers, G.K. Krieglstein; Inhibition of Conjunctival Wound Healing in Rabbits using Synergistic Acting Cytotoxic Drugs . Invest. Ophthalmol. Vis. Sci. 2004;45(13):919.
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Purpose: The process of wound healing following trabeculectomy involves Tenon and episcleral fibroblasts as target cells. This process is one of the most important factors that distinguish between a surgical success or failure. Current clinical concepts mainly involve antifibroblastic substances or, more recently, agents that interfere with specific growth factors. The idea of combining two different cytotoxic and /or apoptotic substances has the intention to reduce the amount of each single substance needed. This may then possibly reduce the rate of side–effects, which are usually associated with the use of high concentrations of cytotoxic drugs in glaucoma filtering surgery. Methods: Female chinchilla bastard rabbits were used and trabeculectomies performed. The site of trabeculectomy was treated for 5 min. with combinations of each two substances including staurosporine, doxorubicin, lomustine, CD95L and mitomycin. Combinations and concentrations of the drugs were choosen from the results of previous cell culture experiments. Operated eyes were enucleated and processed for histopathologic examination at two and four weeks following surgery. Serial sections through the surgical site were performed to determine the amount of wound healing and conjunctival scarring. There were four eyes in each group. Controls included trabeculectomies with no additional cytotoxic substances and trabeculectomies performed with mitomycin (0.5mg/ml) alone. Results: At two weeks, all eyes showed scarring of the trabeculectomy site, the episclera and conjunctiva to a variable extent. Filtering blebs were only seen in those eyes that had received a combination of substances that consisted partially of mitomycin. The control eyes with mitomycin alone did not show a functioning filtering bleb, but had only mild episcleral scarring. At four weeks following surgery, all eyes showed occlusion of the fistula by scarring which was most pronounced in the eyes treated without mitomycin. Conclusions: The idea presented here is a new approach to possibly interfere with post–operative fibroblast proliferation. In contrast to the results of previous tissue culture studies, combinations of cytotoxic drugs that did not include mitomycin were not successful in the animal model.
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