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F. C. Erdurman, H. J. Kaplan, T. H. Tezel; Safety of Intravitreally Injected Immunomodulator Drugs. Invest. Ophthalmol. Vis. Sci. 2009;50(13):6239.
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Immunomodulation has been found to be effective in the treatment of many patients with autoimmune uveitis resistant to corticosteroids. The intraocular use of these drugs may be beneficial and avoid associated systemic toxicity. We determined the effect of intravitreally injected cytotoxic and immunomodulator drugs on retinal cell viability in vitro.
Freshly enucleated adult domestic pig eyes were obtained from a local slaughterhouse. Isolated sensory retinas were cut into small pieces and incubated at 37 °C in the presence of Leflunomide (100 µg/mL), 6-mercaptopurine (50 µg/mL), Tacrolimus (40 µg/mL), Sirolimus (60 ng/mL), Cyclophosphamide (5 µg/mL), and Chlorambucil (0.65 µg/mL). At time points ranging between 1-120 hours retinal cell viability was determined using a Live-Dead viability kit. Untreated retina samples were used as controls. Pairwise Multiple Comparison Procedures (Bonferroni t-test) were used to compare the retinal cell viability results at different time points.
Apart from Leflunomide and Sirolimus (p>0.05), all tested drugs resulted in significant cell viability losscompared to controls. On day 5, toxic effect was highest with Cyclophosphamide (37.7 ± 7.4% vs. 79.3 ± 1.2%, p<0.01) and Chlorambucil (44.0 ± 10.1%, p<0.01), followed by 6-mercaptopurine (56.7 ± 3.1%, p=0.009) and Tacrolimus (60.0 ± 7.0%, p=0.034).
Several cytotoxic and immunomodulator drugs tested in this study adversely effect retinal cell viability in vitro. Leflunomide and Sirolimus were relatively well tolerated. In vivo study of the most promising biologic pharmaceuticals are underway.
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