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Tadao Maeda, Akiko Maeda, Ikuyo Maruyama, Kei-ichi Ogawa, Yoshio Kuroki, Hiroeki Sahara, Noriyuki Sato, Hiroshi Ohguro; Mechanisms of Photoreceptor Cell Death in Cancer-Associated Retinopathy. Invest. Ophthalmol. Vis. Sci. 2001;42(3):705-712.
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purpose. In a previous study, both recoverin and heat shock cognate protein (hsc)
70 were recognized as autoantigens by sera from patients with
cancer-associated retinopathy (CAR), and retinal dysfunction similar to
CAR was inducible by intravitreous injection of anti-recoverin and
anti-hsc 70 antibodies to Lewis rat. The purpose of the present study
was to elucidate the effects of these antibodies on retinal
photoreceptor cell functions, the contribution of caspase during the
photoreceptor degeneration, and the roles of aberrant expression of
recoverin in tumor cells.
methods. As photoreceptor functions, rhodopsin phosphorylation using freshly
prepared rod outer segments (ROS) and electroretinogram (ERG) were
studied. Expression of recoverin in several kinds of tumors was
examined by reverse transcription–polymerase chain reaction and
Western blot analysis. The effects of recoverin on calcium-dependent
protein phosphorylation were studied using the A549 lung adenocarcinoma
cell line, which does not express recoverin.
results. Rhodopsin phosphorylation in bovine ROS was significantly promoted by
the addition of anti-recoverin antibody. Similar effects on rhodopsin
phosphorylation and ERG impairment were observed in rat eyes treated
with anti-recoverin antibody. Co-injection of caspase inhibitors with
anti-recoverin antibody inhibited ERG impairment and significantly
suppressed the antibody-induced enhancement of rhodopsin
phosphorylation. Aberrant expression of recoverin was found in 15 of 30
tumor tissues from patients with cancer without CAR. Profiles of
calcium-dependent protein phosphorylation of cell lysate from A549
cells were modulated by the presence of purified recoverin.
conclusions. These observations suggest that anti-recoverin antibody is incorporated
into rod photoreceptor cells and modulates rhodopsin phosphorylation,
which in turn produces activation of caspase-dependent apoptotic
pathways. Regarding antibody generation in CAR, a high incidence of
aberrant expression of recoverin in cancer tissues is important, as
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