PURPOSE: To determine whether recombinant human interferon alpha-2a (IFN alpha-2a) would diffuse into the choroid in significant amounts from a retrobulbar depot. METHODS: One million international units of IFN alpha-2a were injected into the retrobulbar space of the eyes of 17 rabbits, and choroidal and serum concentrations were measured at 1, 2, 4, 8, 12, and 24 hours. The same dose of IFN alpha-2a was injected subcutaneously into 10 rabbits, and choroidal and serum concentrations were measured at the same intervals for comparison. Parabulbar and ocular tissues were studied by light microscopy for evidence of local toxicity. RESULTS: Peak concentration IFN alpha-2a in the choroid after retrobulbar injection occurred at 2 hours and averaged 32,000 IU/mg. Peak concentration in the serum occurred at 4 hours and averaged 227 IU/ml. Concentrations in choroid and serum fell rapidly, and IFN alpha-2a was not detectible at 24 hours. No IFN alpha-2a was detected in the choroid of the paired eye, and only a trace (< 50 IU/mg) was found in either eye after subcutaneous injection. Light microscopy revealed some lymphocytes in the fat adjacent to the retrobulbar depot after six daily injections of IFN alpha-2a or saline. Sclera, choroid, and retina appeared unaffected. CONCLUSIONS: IFN alpha-2a diffuses into the choroid from a retrobulbar depot in significant amounts. The serum concentration from a retrobulbar injection is < 1% of the choroidal concentration. The retrobulbar route to the choroid may be optimal for testing the effect of IFN alpha-2a on choroidal neovascularization.
PURPOSE: To determine whether recombinant humaninterferon alpha-2a (IFN alpha-2a) would diffuse into the choroid in significant amounts from a retrobulbar depot. METHODS: One million international units of IFN alpha-2a were injected into the retrobulbar space of the eyes of 17 rabbits, and choroidal and serum concentrations were measured at 1, 2, 4, 8, 12, and 24 hours. The same dose of IFN alpha-2a was injected subcutaneously into 10 rabbits, and choroidal and serum concentrations were measured at the same intervals for comparison. Parabulbar and ocular tissues were studied by light microscopy for evidence of local toxicity. RESULTS: Peak concentration IFN alpha-2a in the choroid after retrobulbar injection occurred at 2 hours and averaged 32,000 IU/mg. Peak concentration in the serum occurred at 4 hours and averaged 227 IU/ml. Concentrations in choroid and serum fell rapidly, and IFN alpha-2a was not detectible at 24 hours. No IFN alpha-2a was detected in the choroid of the paired eye, and only a trace (< 50 IU/mg) was found in either eye after subcutaneous injection. Light microscopy revealed some lymphocytes in the fat adjacent to the retrobulbar depot after six daily injections of IFN alpha-2a or saline. Sclera, choroid, and retina appeared unaffected. CONCLUSIONS: IFN alpha-2a diffuses into the choroid from a retrobulbar depot in significant amounts. The serum concentration from a retrobulbar injection is < 1% of the choroidal concentration. The retrobulbar route to the choroid may be optimal for testing the effect of IFN alpha-2a on choroidal neovascularization.
Authors: Y De Kozak; B Thillaye-Goldenberg; M-C Naud; A Vianna Da Costa; C Auriault; C Verwaerde Journal: Clin Exp Immunol Date: 2002-11 Impact factor: 4.330