Histopathological study of the retina in an experimental animal model of retinal damage and in human retinitis pigmentosa.

摘要

Photoreceptors degenerate in a variety of diseases. The most common inherited retinal degeneration is retinitis pigmentosa (RP). This study investigated the anatomy of an animal model of photoreceptor degeneration, and the anatomical changes in the human RP retina. The goal of this study was explore the usefulness of the residual histology for testing treatment strategies such as retinal prostheses.; Part 1 investigated retinal degeneration in the rabbit following systemic iodoacetic acid (IAA) injection. Eyes were examined at 14 days, 1 month, 3 months and 6 months, using standard histology and immunohistochemistry. Although the damage was variable, it was most common in the visual streak (35% of eyes) and ventral retina (43% of eyes), with a significant reduction or elimination of the outer nuclear layer where photoreceptor nuclei are normally found. The inner retina remained intact, as judged by the presence of rod bipolar cells, horizontal cells and Muller cells.; Part 2 examined the labeling pattern of specific cell markers in human retinae with RP. Chx10 and nestin are progenitor cell markers that persist in adult bipolar and Muller cells respectively. Antibodies for protein kinase C-alpha, glial fibrillary acidic protein, and phosphorylated neurofilaments (SMI31) are markers for rod bipolar cells, Muller cells, and retinal ganglion cell axons respectively. Specimens from 10 donors with RP were examined. Chx10-positive cells remained in RP, even where retinal degeneration was severe. Nestin normally labels the endfoot of Muller cells, but in RP nestin was upregulated throughout the Muller cell cytoplasm. Rod bipolar cells were present and particularly disorganized near migrating pigment epithelium cells. Retinal ganglion cell axons ran horizontally, as in normal retina. Thus, despite significant degeneration of RP retina, certain characteristics of the surviving inner retinal cells were preserved.; Iodoacetic acid and retinitis pigmentosa are different models of photoreceptor degeneration. After IAA treatment the surviving inner retina remains well organized. In RP the inner retina becomes disorganized. While the patterns of degeneration in human RP shows the limitations of the rabbit model, the discrete and controlled photoreceptor pathology of the IAA model should be useful for testing treatment strategies such as retinal prostheses.