Experimental, cancer-induced retinopathy

Abstract

Autoantibody reactions with various ocular components have been described in different types of paraneoplastic vision loss, and are considered indicators of an activated, and potentially harmful immunologic process. To date, only one subgroup, the 23 kd CAR syndrome, has been linked with hypersensitivity to a single defined retinal protein, recoverin. Inquiries into the cause of this unusual immunologic reaction led to the discovery that this photoreceptor component is expressed by some, but not all small cell carcinomas, the neoplasm most often linked with paraneoplasias. Neoplasia expressing retinal antigens, outside normal distribution, may provoke an immune response resulting in a cancer-induced autoimmune retinopathy, a cause and effect relationship addressing the etiology and pathogenesis of the CAR syndrome. Since only a subset of paraneoplastic retinopathy patients produce autoantibodies reactive with the 23 kd CAR autoantigen, a search was initiated in other subgroups, seeking additional examples of this immunologic cancer connection.

Cultures of small cell lung carcinomas were obtained from the American Type Culture Collection, Human Tumor Bank (ATCC, HTB), each expressing the unique characteristics of the donor. The ability of single cultures to incite the production of anti-retinal antibodies in laboratory animals was investigated through intraperitoneal propagation in ‘Pristane’ induced ascites, followed by an evaluation of the resultant immunologic response.

A culture of small cell carcinoma of the lung, the HTB 175, was found actively expressing a novel retinal protein corresponding in Western blot analyses to that involved in the autoantibody reactions of an immunologically distinct subgroup of paraneoplastic retinopathy patients.

Key Words:

• Cancer
• retinopathy
• immune-mediated
• non-inflammatory