Cancer-associated retinopathy induced by both anti-recoverin and anti-hsc70 antibodies in vivo.
OBJECTIVE
In a previous study, both recoverin and heat shock cognate protein 70 (hsc 70) were found as autoantigens recognized by sera from four patients with cancer-associated retinopathy (CAR). This observation suggested that autoimmune reactions against recoverin and hsc 70 might be involved together in the pathogenesis of CAR. The purpose of the present study is to investigate the effects of these autoantibodies on retinas in vivo.


METHODS
Functional and morphologic properties of the retinas were evaluated after anti-recoverin and/or anti-hsc 70 antibodies were intravitreously injected into Lewis rats' eyes.


RESULTS
Responses in electroretinogram (ERG) of eyes penetrated with anti-hsc 70 antibody were comparable with the control, but those with anti-recoverin antibody were remarkably reduced during the 3-week period after the injection. Such anti-recoverin antibody-induced reduction was significantly enhanced by copenetration with anti-hsc 70 antibody. Immunofluorescence microscopy demonstrated that after intravitreal injection, anti-recoverin antibody penetrated toward the outer nuclear layer (ONL) and outer segments within 12 to 24 hours, and the presence of the antibody in the retina diminished during the next few days. Histopathology revealed significant thinning of the ONL and inner nuclear layer (INL) in the affected retina in comparison with the control. Throughout the ONL and INL, apoptotic cells were recognized by TdT-dUTP terminal nick-end labeling. The antibody-induced retinal dysfunction was effectively treated by administrations of either corticosteroid or cyclosporin A.


CONCLUSIONS
These observations suggest that anti-recoverin- and anti-hsc 70 antibody-induced retinal dysfunction in Lewis rat is a good model to study the pathophysiology of CAR.
Ohguro
H
H
Department of Ophthalmology, Sapporo Medical University School of Medicine, Japan. ooguro@sapmed.ac.jp
Ogawa
K
K
Maeda
T
T
Maeda
A
A
Maruyama
I
I
D000818:Animals; D001323:Autoantibodies / Q000494:pharmacology*; D015153:Blotting, Western; D002135:Calcium-Binding Proteins / Q000276:immunology*; D002352:Carrier Proteins / Q000276:immunology*; D002417:Cattle; D004338:Drug Combinations; D004596:Electroretinography / Q000187:drug effects; D005136:Eye Proteins; D019084:Fluorescent Antibody Technique, Indirect; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000276:immunology; D051597:Hippocalcin; D007074:Immunoglobulin G / Q000494:pharmacology; D020287:In Situ Nick-End Labeling; D008074:Lipoproteins; D009419:Nerve Tissue Proteins; D010257:Paraneoplastic Syndromes / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D011917:Rats, Inbred Lew; D051603:Recoverin; D012160:Retina / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D012164:Retinal Diseases / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology
D001323:Autoantibodies; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D004338:Drug Combinations; D005136:Eye Proteins; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; C494373:Hspa8 protein, rat; D007074:Immunoglobulin G; D008074:Lipoproteins; D009419:Nerve Tissue Proteins; C496733:Rcvrn protein, rat; D051603:Recoverin; D051597:Hippocalcin