Pathological roles of recoverin in cancer-associated retinopathy.
Cancer associated retinopathy (CAR) is an ocular manifestation of paraneoplastic syndrome clinically characterized by progressive visual impairment similar to retinitis pigmentosa. As a possible mechanism causing the retinal degeneration, the presence of serum autoantibodies against recoverin and other retinal antigens are involved. The molecular pathology in CAR by anti-recoverin antibody is considered to occur in the following steps: Firstly, recoverin aberrantly expressed in cancerous tissues is recognized by immunocytes by some unknown mechanisms and then a specific antibody toward recoverin is produced. Secondly, the anti-recoverin antibody reaches the retina via the peripheral circulation and is taken up into photoreceptor cells. Lastly, the antibody blocks recoverin function (inhibition of rhodopsin phosphorylation in a calcium dependent manner), and enhancement of rhodopsin phosphorylation induces retinal apoptosis.
Ohguro
Hiroshi
H
Department of Ophthalmology, Hirosaki University School of Medicine, 5 Zaifu-cho, Hirosaki 036-8652, Aomori, Japan. ooguro@cc.hirosaki-u.ac.jp
Nakazawa
Mitsuru
M
D000368:Aged; D000595:Amino Acid Sequence; D000818:Animals; D001324:Autoantigens / Q000737:chemistry; D015153:Blotting, Western; D002135:Calcium-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D005136:Eye Proteins; D005260:Female; D051597:Hippocalcin; D006801:Humans; D008027:Light; D008074:Lipoproteins; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000150:complications* / Q000378:metabolism / Q000628:therapy; D009419:Nerve Tissue Proteins; D010257:Paraneoplastic Syndromes / Q000209:etiology / Q000378:metabolism* / Q000628:therapy; D051381:Rats; D051603:Recoverin; D012164:Retinal Diseases / Q000209:etiology / Q000378:metabolism* / Q000628:therapy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013997:Time Factors
D001324:Autoantigens; D002135:Calcium-Binding Proteins; D005136:Eye Proteins; D008074:Lipoproteins; D009419:Nerve Tissue Proteins; C496731:RCVRN protein, human; C496733:Rcvrn protein, rat; D051603:Recoverin; D051597:Hippocalcin