Effects of daunorubicin and CD95L on retinal function in superfused vertebrate retina.

Alternative treatments of proliferative vitreoretinopathy (PVR) are needed. The intravitreal application of daunorubicin combined with CD95 ligand (CD95L) could provide a new therapeutic strategy. The effects of this application on bovine retinal function were investigated. Bovine retina preparations were perfused with a standard solution preequilibrated with oxygen. The b-wave and, after the addition of aspartate, the photoreceptor potential P III of the electroretinogram (ERG) were recorded using Ag/AgCl electrodes. Stable ERG amplitudes were recorded, then daunorubicin was added to the solution for 45 minutes, also with the addition of CD95L antibody. Subsequently, the preparation was reperfused with the standard solution for 100 minutes, to allow for recovery. The reduction in b-wave amplitude was reversible and not significantly changed by the addition of 0.25 microg/mL CD95L antibody to 13 microM of daunorubicin. The reduction of the b-wave amplitude was significantly changed and only partly reversible within the recovery time using 40 microM and 80 microM of daunorubicin. The photoreceptor potential P III amplitude was not significantly changed for up to 80 microM of daunorubicin. The ERG showed toxic effects of daunorubicin above a concentration of 13 microM used therapeutically in humans. The combination with CD95L did not increase retinal toxicity. It is, therefore, concluded that daunorubicin may be applied intraocularly, combined with CD95L, without interfering with retinal function.