title: Retinal dysfunction in cancer-associated retinopathy is improved by Ca(2+) antagonist administration and dark adaptation.
abstract: OBJECTIVE
  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 Ca(2+) 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 Ca(2+) 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 Ca(2+) antagonist.
authors.affiliation: Department of Ophthalmology, Hirosaki University School of Medicine, Japan. ooguro@cc.hirosaki-u.ac.jp
authors.forename: H
authors.initials: H
authors.lastname: Ohguro
authors.forename: K
authors.initials: K
authors.lastname: Ogawa
authors.forename: T
authors.initials: T
authors.lastname: Maeda
authors.forename: I
authors.initials: I
authors.lastname: Maruyama
authors.forename: A
authors.initials: A
authors.lastname: Maeda
authors.forename: Y
authors.initials: Y
authors.lastname: Takano
authors.forename: M
authors.initials: M
authors.lastname: Nakazawa
mesh_terms: D000818:Animals; D000906:Antibodies / Q000008:administration & dosage; D000951:Antigens, Neoplasm / Q000276:immunology; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D002135:Calcium-Binding Proteins / Q000276:immunology; D003623:Dark Adaptation; D004596:Electroretinography; D005136:Eye Proteins; D051597:Hippocalcin; D007267:Injections; D007274:Injections, Intraperitoneal; D008027:Light; D008074:Lipoproteins; D009419:Nerve Tissue Proteins; D009543:Nifedipine / Q000031:analogs & derivatives / Q000627:therapeutic use*; D010257:Paraneoplastic Syndromes / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D010766:Phosphorylation; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism / Q000473:pathology; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D051603:Recoverin; D012164:Retinal Diseases / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D012243:Rhodopsin / Q000378:metabolism; D014822:Vitreous Body
chemical_list: D000906:Antibodies; D000951:Antigens, Neoplasm; D002121:Calcium Channel Blockers; D002135:Calcium-Binding Proteins; D005136:Eye Proteins; D008074:Lipoproteins; D009419:Nerve Tissue Proteins; C496733:Rcvrn protein, rat; C035100:nilvadipine; D051603:Recoverin; D051597:Hippocalcin; D012243:Rhodopsin; D009543:Nifedipine