Retinal pigment epithelial hypersensitivity, an association with vision loss: RPE hypersensitivity complicating paraneoplastic retinopathies

Abstract

PURPOSE: Paraneoplastic retinopathies are currently identified and classified according to specific anti-retina antibody reactions. These cancer-induced retinal degenerations can be accompanied by changes in the character of the retinal pigment epithelium (RPE) indicative of additional, and superimposed, pathologic activity. The antibody reactions of 11 paraneoplastic retinopathy patients were evaluated to identify those whose immunologic abnormalities included indications of RPE hypersensitivity. The pathologic significance of this anomaly was evaluated upon viable monolayers of RPE, in the presence and absence of complement. METHODS: Comparisons of antibody reactions were made using: (1) indirect immunohistochemistry on sections of rhesus monkey eyes; (2) Western blot reactions on extracts of rhesus monkey retina and in vitro-propagated rhesus RPE; and (3) an evaluation of antibody influence upon the metabolic activity of viable monolayers of rhesus RPE cells. RESULTS: Indirect immunohistochemistry on sections of monkey eyes identified antibodies reactive with RPE in four of the 11 cancer patients. The same four were found to identify a 57 kd protein component of these cells in Western blot reactions of RPE and to inhibit the metabolic activity of viable RPE cells through actions enhanced by the addition of complement. One subject from the reference comparison control group, a cancer-free patient with age-related macular degeneration, also exhibited comparable antibody activity with RPE. CONCLUSIONS: RPE hypersensitivity can present as a superimposed immunologic complication to the retinal degenerations of paraneoplastic retinopathies and those unrelated to malignancies. When activated, humoral aspects of the immune response are able to impart pathologic effects that inhibit RPE homeostasis and, consequently, the essential supportive functions of these cells. Since this immunologic abnormality is not confined to cancer patients, it should be considered potentially harmful when encountered in association with any type of vision loss.