| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2000: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1999: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Research Abstract |
A visual paraneoplastic syndrome called cancer-associated retinopathy(CAR) has been identified in patients with small cell carcinoma of lung and other malignant tumors. These patients are clinically characterized with photopsia, progressive visual loss with a ring scotoma, attenuated retinal arterioles, and abnormalities of the a- and b-waves of the ERG.Histopathological and immunological observations revealed that, in CAR, loss of photoreceptor cells may be caused by an autoimmune reaction against a photoreceptor specific 23 kDa calcium binding protein called recoverin. Functionally, recoverin was found to play a major role in light and dark adaptation by regulating rhodopsin phosphorylation and dephosphorylation in a calcium-dependent manner. Recently, expression of recoverin has been identified in the cancer cells of CAR patients, and expression of the CAR antigen(recoverin)is induced by an intraperitoneal cultivation of small-cell carcinoma. These observations allowed us to speculate that aberrant expression of recoverin in cancer cells may trigger an autoimmune reaction. In addition, other retinal antigens including 65 kDa protein, 48 kDa protein, enolase(46 kDa protein), and neurofilament(58-62 kDa, 145 kDa and 205 kDa proteins)are recognized by some CAR patients' sera. Among these retinal autoantigens, recoverin alone or a combination of recoverin and 65 kDa protein have most frequently been shown as the immunoreactive bands in western blot analysis in the previous reports. Most recently our group identified the 65 kDa protein as heat shock cognate protein 70(hsc 70). Therefore, we suggested that both anti-recoverin and anti-hsc 70 antibodies are involved in the pathogenesis of CAR.In the present study, to further investigate the pathological roles of anti-recoverin and anti-hsc 70 antibodies in CAR, we injected these antibodies into the vitreous cavity of Lewis rats, and performed histopathological and electrophysiological characterization of the retinas.
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