Chx10 and Nestin Labeling in Retinitis Pigmentosa Retina

Abstract

Purpose:: This work is related to the efforts of the Boston Retinal Implant Project to develop a sub-retinal prosthesis to restore vision to the blind. The specific purpose of this presentation is to determine the expression pattern of Chx10 and nestin in retinae with retinitis pigmentosa (RP). Chx10 is a homeobox gene, which is important in development of the mammalian eye, and nestin is a large intermediate filament protein, found in the most primitive neuroepithelium. Chx10 and nestin are neural progenitor cell markers in the developing retina. However, these markers persist in bipolar cells and Müller cells respectively in the normal adult retina. Our goal was to determine whether these markers are still expressed in the retina after the remodeling of bipolar cells and Müller cells that occurs in RP.

Methods:: Specimens from 10 donors with RP were examined. The specimens were obtained from the Foundation Fighting Blindness, and contained a wide range of pathology. Immunoreactivity for Chx10 and nestin was studied using frozen sections and standard immunohistochemistry. Chx10 labeling and nestin labeling was compared to PKC (for rod bipolar cells) and GFAP (for Müller cells) in the same specimens.

Results:: Chx10- and nestin-positive cells were still present in the RP retinae, even at locations where retinal degeneration and retinal pigment epithelial cell migration were severe. In cases in which the outer retina had completely degenerated the Chx10-positive cells abutted the retinal pigment epithelium. Nestin appeared to be expressed in Müller cell cytoplasm in both RP and normal human retina. In addition, some nestin-positive cell bodies were seen in the RP retinae that were GFAP-negative. These cells were not seen in normal retina.

Conclusions:: Despite massive rearrangements of cells, and the obliteration of normal structure in the advanced RP retina, Chx10 continues to be expressed in a subpopulation of the remaining cells. In normal retina, it has been suggested that persistent expression of Chx10 helps to maintain the bipolar cell phenotype, and this may be the case in RP as well. Likewise, nestin is a constituent of normal Müller cells and expression persists in the hypertrophic Müller cells of the RP retina. The nestin-positive, GFAP-negative cells seen in the RP retinae were rare and may represent an adaptive response to the remodeled environment.

Keywords: immunohistochemistry • pathology: human • retinal degenerations: hereditary