HISTOPATHOLOGY AND IMMUNOCYTOCHEMISTRY OF THE NEUROSENSORY RETINA IN FUNDUS FLAVIMACULATUS

Background: Fundus flavimaculatus (Stargardt disease) is a group of in herited macular dystrophies in which central vision usually decreases in the first two decades of life. Previous histopathologic studies use d light; scanning, and transmission electron microscopy to characteriz e the retinal pigment epithelium (RPE) in fundus flavimaculatus. The a uthors describe in detail the pathologic changes in the neurosensory r etina, including use of specific immunocytochemical markers. Methods: The eyes of a patient with fundus flavimaculatus were processed using Medcast and JB-4 plastic for light and electron microscopy, and cryomi crotomy and LR-white resin for immunocytochemistry. Results: Changes i n the RPE occurred in a peripheral/central gradient and included incre ased lipofuscin content and cell loss toward the macula. The changes i n the retina paralleled those in the RPE, including accumulation of li pofuscin in photoreceptor inner segments, loss of photoreceptors, and reactive Miller cell hypertrophy. Immunocytochemistry using rod- and c one-specific markers showed abnormal photoreceptor morphology but qual itatively normal immunoreactivity, and there was strong reactivity for glial fibrillary acid protein in reactive Muller cells. Labeling for cellular retinaldehyde-binding protein was qualitatively normal in Mul ler cells, but was reduced in RPE cells that were engorged with lipofu scin. Conclusions: The histopathologic changes in the retina correlate with clinical progression of the disease process. Although abnormal l ipofuscin metabolism has been implicated in the loss of vision in fund us flavimaculatus and other macular diseases, the mechanism is not und erstood. Based on the authors' observations and a review of recent lit erature on lipofuscin, the authors propose that all-trans-retinol dehy drogenase, a photoreceptor outer segment enzyme, may be defective in f undus flavimaculatus.