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(Investigative Ophthalmology and Visual Science. 2001;42:2589-2595.)
© 2001 by The Association for Research in Vision and Ophthalmology, Inc.

Retinal Dysfunction in Cancer-Associated Retinopathy Is Improved by Ca2+ Antagonist Administration and Dark Adaptation

Hiroshi Ohguro1, Kei-ichi Ogawa2, Tadao Maeda2, Ikuyo Maruyama1, Akiko Maeda2, Yoshiko Takano1 and Mitsuru Nakazawa1

1 From the Department of Ophthalmology, Hirosaki University School of Medicine, Japan; and the 2 Department of Ophthalmology, Sapporo Medical University School of Medicine, Japan.

PURPOSE. It was recently found that recoverin acts as an autoantigen recognized by sera of patients with cancer-associated retinopathy (CAR), and that CAR-like retinal dysfunction is produced by intravitreous administration of anti-recoverin antibody in Lewis rat eyes. To examine the pathologic molecular mechanism of CAR, and to elucidate an effective therapy for CAR, the function and morphology of CAR were compared with those of phototoxic retinal damage, another form of photoreceptor dysfunction, and the effect of nilvadipine, a Ca2+ antagonist, on the retinal degenerations was studied, using these models.

METHODS. Under different illumination conditions and/or medication with nilvadipine, the functional and morphologic properties of the retinas were evaluated after intravitreous injection of anti-recoverin antibody into Lewis rat eyes (six rats, 12 eyes in each experimental condition), using electroretinogram (ERG), rhodopsin phosphorylation, and light microscopy.

RESULTS. Anti-recoverin antibody administered into the vitreous of Lewis rat eyes induced a significant decrease and increase of ERG responses and rhodopsin phosphorylation levels, respectively, under cyclic or continuous light. Similar changes were observed in eyes of rats bred under continuous illumination that did not receive anti-recoverin antibodies. However, anti-recoverin antibody–induced retinal dysfunctions were not observed in rat eyes under dark conditions. Administration of nilvadipine, a Ca2+ antagonist, to the anti-recoverin antibody–treated rats and rats with phototoxic retinal dysfunction caused significant improvement of the deterioration of ERG and normalization of rhodopsin phosphorylation.

CONCLUSIONS. The present data indicate that anti-recoverin antibody–induced retinal dysfunction was functionally similar to phototoxic retinal dysfunction and was markedly suppressed under dark conditions or by systemic administration of a Ca2+ antagonist.




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F. Ishikawa, H. Ohguro, I. Ohguro, H. Yamazaki, K. Mamiya, T. Metoki, T. Ito, Y. Yokoi, and M. Nakazawa
Prolonged Rhodopsin Phosphorylation in Light-Induced Retinal Degeneration in Rat Models
Invest. Ophthalmol. Vis. Sci., December 1, 2006; 47(12): 5204 - 5211.
[Abstract] [Full Text] [PDF]




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