Cancer-associated retinopathy (CAR), characterized by
photopsia, progressive visual loss with a ring scotoma, attenuated
retinal arterioles, and abnormalities of the a- and b-waves of
ERG,
1 has been recognized in patients with small-cell
carcinoma of the lung and other malignant tumors.
2 3 4 5 6 7 8 Based on histopathologic and immunologic studies, it has been suggested
that in CAR, photoreceptor loss is primarily caused by an autoimmune
reaction against a photoreceptor-specific 23-kDa calcium-binding
protein, recoverin.
9 10 Functionally, recoverin has been
identified as playing a major role in light and dark adaptation by
regulating rhodopsin phosphorylation and dephosphorylation in a
calcium-dependent manner.
11 12 Aberrant expression of
recoverin has been identified in cancer cells of several patients,
including those with CAR,
13 14 15 16 17 suggesting that aberrant
expression of recoverin in cancer cells may trigger an autoimmune
reaction. In addition, other retinal antigens including a 65-kDa
protein,
18 19 20 a 48-kDa protein,
8 enolase
(46-kDa protein),
21 and neurofilament (58–62-kDa,
145-kDa, and 205-kDa proteins)
22 are also recognized by
sera of some patients with CAR. Among these retinal autoantigens, we
have identified the 65-kDa protein as heat shock cognate protein 70
(hsc70)
20 and have found that CAR-like retinal dysfunction
is produced by intravitreal injection of anti-recoverin antibody and
that this anti-recoverin–induced retinal dysfunction is worsened by
coadministration with anti-hsc70 antibody in Lewis rats.
23 Therefore, we suggest that autoimmune reactions to recoverin and hsc70
play significant roles in the pathologic molecular mechanisms of CAR.