We evaluated the cytotoxicity of four aminoglycoside agents (neomycin, gentamicin, tobramycin, and amikacin) using an in vitro confluent rabbit corneal epithelial cell culture model. Primary corneal epithelial cell cultures were established and cells replated at 2 x 10(4) cells/2 cm2 well. After 48 hours either vehicle or an antibiotic was added at varying concentrations, each for 5, 30, or 60 minutes. 3H-thymidine was added immediately after drug removal and incorporation was measured 8 hours after drug or vehicle exposure. Comparisons of each drug to vehicle were expressed as % inhibition of control culture values. At the 5-minute exposure time tobramycin and amikacin showed no significant inhibition at any concentration, whereas neomycin and gentamicin showed significant inhibition at 6 mg/ml and 3.5 mg/ml or greater concentrations, respectively (p less than 0.05). At 30- and 60-minute exposure times all agents demonstrated significant inhibition at all tested concentrations in a non-dose dependent fashion (p less than 0.05). These in vitro data corroborate the animal and limited clinical data available for the aminoglycosides. Based on these toxicity profiles, tobramycin appears to be the topical agent of choice in the treatment of susceptible bacterial keratitis.
Fibroblast proliferation with subsequent bleb scarring is a major cause of filtering surgery failure. To investigate possible antiproliferative effects of beta radiation, owl monkey Tenon's capsule fibroblasts in tissue culture were irradiated to doses of 30, 100, 300, 1,000, and 3,000 rads with a linear accelerator and to doses of 95,285, and 950 rads with a Strontium-90 applicator. The irradiated cell proliferation expressed as the percentage of the non-irradiated control growth on the third and seventh days, respectively, after beta irradiation was: 97% and 96% after 30 rads; 72% and 90% after 100 rads; 48% and 44% after 300 rads; 39% and 14% after 1,000 rads; and 39% and 14% after 3,000 rads. Similar effects on cell proliferation were observed with the Strontium-90 applicator. The inhibitory effect of beta irradiation on fibroblast proliferation in tissue culture suggests that beta irradiation after filtering surgery may reduce postoperative bleb scarring.
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