Inhibition of Tenon's fibroblast proliferation and enhancement of filtration surgery in rabbits with cytosine arabinoside.
Our purpose was to study the antiproliferative effect of cytosine arabinoside (Ara-C) on rabbit Tenon's fibroblasts and the efficacy of Ara-C as an adjunctive antifibrosis treatment for glaucoma filtration surgery in the rabbit eye. Rabbit Tenon's fibroblasts were exposed to 1 microg/ml of Ara-C for various time intervals, then cell number and viability was assessed at different time points. Following posterior lip sclerectomy, rabbit eyes were treated with 10 mg subconjunctival Ara-C daily for 7 days, then every other day for 7 days. Rabbit fibroblasts exposed to 1 microg/ml Ara-C for 1 hour showed no significant decrease in cell number compared with control. Continuous or 24-hour incubation of fibroblasts with Ara-C was lethal to the cells. Exposure of cells to Ara-C for 3-, 6-, and 9-hour intervals caused significant reduction of cell proliferation. Pulsed treatment of cells with 6 hour exposure to 1 microg/ml Ara-C every 3 days caused prolonged suppression of cell proliferation. Following posterior lip sclerectomy in rabbits, topical instillation of Ara-C drops at varying concentrations and dosing intervals did not cause any significant lowering of intraocular pressure compared with control eyes, although bleb survival was prolonged in eyes treated with Ara-C (P < 0.01). In rabbit eyes treated postoperatively with subconjunctival injections of 10 mg Ara-C every other day for two weeks, the mean intraocular pressure was significantly decreased and the bleb survival time was significantly prolonged (P < 0.0067) compared with control eyes. In conclusion, Ara-C inhibits rabbit Tenon's fibroblast proliferation in vitro. Postoperative subconjunctival injection of Ara-C results in improved bleb function after filtration surgery in the rabbit.
Department of Ophthalmology, University of Tennessee, Memphis 38163, USA.
L A
LA
Al-Aswad
M
M
Huang
P A
PA
Netland
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000494:pharmacology*; D002452:Cell Count / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003228:Conjunctiva / Q000166:cytology / Q000187:drug effects*; D003238:Connective Tissue; D003239:Connective Tissue Cells / Q000187:drug effects*; D003561:Cytarabine / Q000008:administration & dosage / Q000494:pharmacology*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D005355:Fibrosis / Q000517:prevention & control; D018463:Filtering Surgery; D007429:Intraocular Pressure / Q000187:drug effects; D011817:Rabbits
D000964:Antimetabolites, Antineoplastic; D003561:Cytarabine