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M. M. Hermann, B. Schröter, M. Diestelhorst; Effect of Rapamycin on Postoperative Fibrosis After Filtration Surgery in a Rabbit Model. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3910.
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Postoperative fibrosis is still a major threat for successful filtration surgery in glaucoma. Currently used agents used to modulate wound healing (e.g. Mitomycin C) are known to cause significantly toxic effects on ocular tissue. Rapamycin (Sirolimus) has a known antifibrotic action on vascular endothelium und cultured fibroblasts. This study aimed at evaluating the effects of Rapamycin on postoperative fibrosis after filtration surgery in a rabbit model.
Cultured primary human tenon fibroblasts were exposed to Rapamycin (5-1000 ng/ml) and compared to untreated fibroblasts using a standardized scratch-assay. 12 rabbits (ChBB:CH; n=12) received a unilateral subconjunctival injection of Rapamycin (200µl, 1mg/ml) after filtrating glaucoma surgery. 12 control eyes received a subconjunctival injection of PBS after surgery. Antifibrotic efficacy was established by clinical response and histological examination. Clinical response was assessed by comparing intraocular pressure (IOP) between the treated experimental eye and the fellow eye, which served as control. Animals were sacrificed four weeks after surgery for histological examination.
Scratch assays revealed a significantly delayed regeneration of the cell-layer with Rapamycin concentrations of 200 ng/ml and above (cell counts, Mann-Whitney-U-Test, p<0.05). No cytotoxic effects were observed in cell culture experiments using trypan blue staining nor in histology. IOP was significantly decreased on the third postoperative day in eyes with Rapamycin treatment (Student's t-test, p<0.05). These eyes also showed a milder fibrosis in histological examinations compared to control eyes (blinded examination and scoring, Mann-Whitney-U-Test, p<0.05).
Whether a sufficient long-term effect may be achieved with subconjunctival injection of Rapamycin remains to be elucidated. Although safety and reliability certainly demand further studies, Rapamycin is a promising therapeutic approach to control postoperative fibrosis in patients undergoing filtration surgery.
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