Retinal dysfunction in cancer-associated retinopathy is improved by Ca2+ antagonist administration and dark adaptation

PURPOSE. It was recently found that recoverin acts as an autoantigen recogn ized by sera of patients with cancer-associated retinopathy (CAR), and that CAR-like retinal dysfunction is produced by intravitreous administration o f anti-recoverin antibody in Lewis rat eyes. To examine the pathologic mole cular mechanism of CAR, and to elucidate an effective therapy for CAR, the function and morphology of CAR were compared with those of phototoxic retin al damage, another form of photoreceptor dysfunction, and the effect of nil vadipine, a Ca2+ antagonist, on the retinal degenerations was studied, usin g these models. METHODS. Under different illumination conditions and/or medication with nil vadipine, the functional and morphologic properties of the retinas were eva luated after intravitreous injection of anti-recoverin antibody into Lewis rat eyes (six rats, 12 eyes in each experimental condition), using electror etinogram (ERG), rhodopsin phosphorylation, and light microscopy. RESULTS. Anti-recoverin antibody administered into the vitreous of Lewis ra t eyes induced a significant decrease and increase of ERG responses and rho dopsin phosphorylation levels, respectively, under cyclic or continuous lig ht. Similar changes were observed in eyes of rats bred under continuous ill umination that did not receive anti-recoverin antibodies. However, anti-rec overin antibody-induced retinal dysfunctions were not observed in rat eyes under dark conditions. Administration of nilvadipine, a Ca2+ antagonist, to the antirecoverin antibody-treated rats and rats with phototoxic retinal d ysfunction caused significant improvement of the deterioration of ERG and n ormalization of rhodopsin phosphorylation. CONCLUSIONS. The present data indicate that anti-recoverin antibody-induced retinal dysfunction was functionally similar to phototoxic retinal dysfunc tion and was markedly suppressed under dark conditions or by systemic admin istration of a Ca2+ antagonist.