Abstract
Purpose: :
To study the effect of 0.4% Ketorolac tromethamine ophthalmic solution (Acular LS, Allergan, Irvine, California), a topical nonsteroidal anti-inflammatory drug, on human retinal pigment epithelial (ARPE-19) and rat retinal neurosensory (R28) cells in vitro.
Methods: :
ARPE-19 and R28 cells were grown in tissue culture in Dulbecco’s modified Eagle’s medium (DMEM) containing 10% fetal bovine serum. Cells were treated with five different concentrations of Ketorolac (300 µg/ml, 200 µg/ml, 100 µg/ml , 50 µg/ml and 25 µg/ml) for 24 hours. The doses were chosen to bracket the intravitreal clinical dose determined by assuming 0.1 cc of the commercial preparation distributes equally throughout the 4 ml human vitreous volume. Using this approach the calculated clinical dose is 100 µg/ml. Toxicity was determined by a trypan blue dye-exclusion cell viability assay.
Results: :
The mean cell viability of ARPE-19 cells after 24 hours exposure to 300 µg/ml, 200 µg/ml, 100 µg/ml, 50 µg/ml and 25 µg/ml of Ketorolac was: 38.31% ± 11.29 (P < 0.001), 82.4% ± 9.2 (P > 0.05), 96.4% ± 1.42 (P > 0.05), 95.8% ± 2.03 (P > 0.05) and 94.8% ± 3.5 (P > 0.05) respectively, compared to untreated control ARPE-19 cells that had a viability of 96.28 ± 1.5. The mean cell viability of R28 cells exposed to 24 hours of 300 µg/ml, 200 µg/ml, 100 µg/ml, 50 µg/ml and 25 µg/ml of Ketorolac was: 64.4% ± 12.5 (P < 0.001), 93.1% ± 2.7 (P > 0.05), 91.6% ± 3.7 (P > 0.05), 91.3% ± 3.7 (P > 0.05) and 90.5% ± 3.7 (P > 0.05) respectively, compared to untreated control R28 cells that had a viability of 89.46 ± 5.11.
Conclusions: :
These results suggest that Ketorolac at clinically relevant intravitreal doses is not toxic to ARPE-19 and R28 cells in vitro.
Keywords: drug toxicity/drug effects • cell survival • retinal culture