Avisual paraneoplastic syndrome called cancer-associated
retinopathy (CAR) has been identified in patients with small cell
carcinoma of lung and other malignant tumors.
1 2 3 4 5 6 7 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 electroretinogram
(ERG).
8 Histopathologic and immunologic 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.
9 10 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.
11 12 Recently, expression of recoverin has been identified in the cancer
cells of CAR patients,
13 14 and expression of the CAR
antigen (recoverin) is induced by an intraperitoneal cultivation of
small cell carcinoma.
15 16 17 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,
18 19 20 48-kDa
protein,
8 enolase (46-kDa protein),
21 and
neurofilament (58- to 62-, 145-, and 205-kDa proteins)
22 are recognized by some CAR patients’ sera. Among these retinal
autoantigens, recoverin alone
8 23 24 or a combination of
recoverin and 65-kDa protein
18 19 20 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).
20 Therefore, we
suggested that both anti-recoverin and anti-hsc 70 antibodies are
involved in the pathogenesis of CAR.