ABSTRACT
OBJECTIVE@#To study the effect of rapamycin on scar formation in rabbit eyes following filtering operation and explore the possible mechanism.@*METHODS@#Ninety-six healthy adult rabbits were subjected to trabeculectomy of the left eye and subsequently randomly divided into 4 groups (=24) for treatment with castor oil (control) or rapamycin (1%, 3%, or 5%) eye drops of the operated eyes 4 times a day. The morphology and function of the filtering blebs of the rabbits were compared at 7, 14, 21 and 28 days after the operation; at each of the time points, 6 rabbits from each group were euthanized for detection of expressions of proliferating cell nuclear antigen (PCNA) and α-smooth muscle actin (α-SMA) in the tissues in the surgical area using immunohistochemistry. Cultured rabbit subconjunctival fibroblasts (RTFSs) were treated with different concentrations of rapamycin (0.06, 0.25, 1, and 4 mg/L) and the cell apoptosis was detected using flow cytometry.@*RESULTS@#In the first, second and third weeks after the operation, the rate of functional follicle formation was significantly higher in the 3 rapamycin groups than in the control group ( < 0.05), and the number of α- SMA-positive fibroblasts decreased over time in the 3 rapamycin groups. In cultured RTFSs, treatment with rapamycin at different concentrations resulted in increased apoptosis of the cells, and rapamycin above 0.25 mg/L significantly increased the cell apoptosis in a dose-dependent manner.@*CONCLUSIONS@#Rapamycin can inhibit hyperplasia of the filtering passage tissue, helps to preserve the functional filtering blebs and prolong their life span, and induces apoptosis of RTFS.
ABSTRACT
OBJECTIVE@#To study the anti- scarring effect of rapamycin in rabbits receiving glaucoma filtering surgery.@*METHODS@#Ninety-six Chinchilla rabbits were randomized equally into 3 rapamycin treatment groups and one control group. All the rabbits underwent trabeculectomy, after which the rabbits in the 3 rapamycin groups were treated with eye drops containing 1%, 3%, or 5% rapamycin in the operated eyes, and those in the control groups were given castor oil 4 times a day. The intraocular pressure (IOP) and inflammatory reaction in the treated eyes were observed, and the PCNA-positive cells in the filtering bleb were detected using immunohistochemistry. RTFs isolated from the Tenon's capsule of the rabbits were cultured , and the expressions of caspase-3, caspase-8, and caspase-9 in the fibroblasts were detected after treatment with different concentrations of rapamycin.@*RESULTS@#The IOP was significantly lower in rapamycin-treated group than in the control group after the surgery ( < 0.05). The counts of the PCNA-positive cells were significantly lower in rapamycin-treated rabbits than in the control group ( < 0.05). Rapamycin treatment dose-dependently increased the expressions of caspase-3 and caspase- 9 at both the mRNA ( < 0.001) and protein ( < 0.001) levels without causing significant changes in the expressions of caspase-8.@*CONCLUSIONS@#Rapamycin can inhibit excessive proliferation of the fibroblasts in the filtering bleb to reduce scar formation after glaucoma filtration surgery in rabbits. Rapamycin also increases the expressions of caspase-3 and caspase-9 to induce apoptosis of the RTFs.