Abstract

P 108

Antifibrotic action of Rapamycin after filtration surgery in a rabbit model

Manuel Hermann, Benedikt Schröter, Michael Diestelhorst
Zentrum für Augenheilkunde, Klinikum der Universität zu Köln, Köln

Objective
Postoperative fibrosis is still a major threat for successful filtration surgery in glaucoma. Currently used agents used to modulate wound healing (e.g. Mitoymcine C) are known to cause significant toxic effects on ocular tissue. Rapamycin (Sirolimus) has a known antifibrotic action on vascular endothelium und cultured fibroblasts. This study aimed to evaluate effects of Rapamycin on postoperative fibrosis after filtration surgery in a rabbit model.
Methods
Cultured primary human tenon fibroblasts were exposed to Rapamycin (5-1000 ng/ml) and compared to untreated fibroblasts using a standardized scratch-assay. Rabbits (ChBB:CH; n=12) received a unilateral subconjunctival injection of Rapamycine (200µl, 1mg/ml) after filtrating glaucoma surgery. 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.
Results
Scratch assays revealed a significantly retarded regeneration of the cell-layer with Rapamycin concentrations of 200ng/ml and above. No cytotoxic effects were observed in cell culture experiments using trypan blue staining or in histology. IOP was significantly decreased on the third postoperative day in eyes with Rapamycin treatment. These eyes also showed a milder fibrosis in histological exam compared to control eyes.
Conclusions
Whether a sufficient long-term effect may be achieved with subconjunctival injections remains to be seen. Though safety and reliability certainly demand further studies, Rapamycin may be a promising therapeutic approach to control postoperative fibrosis in patients undergoing filtration surgery.

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