Immunohistological Study of Monkey Foveal Retina

Abstract

The fovea centralis, an anatomically concave pit located at the center of the macula, is avascular, hypoxic, and characteristic of stem-cell niches of other tissues. We hypothesized that in the fovea, undifferentiated retinal-stem-cell-like cells may exist, and that neurogenesis may occur. Hence, we performed an immunohistological study using cynomolgus monkey retinas. After preparing frozen tissue sections of the retina including the foveal pit, immunostaining was performed for glial fibrillary acidic protein (GFAP), nestin, vimentin, neuron-specific class III β-tubulin (Tuj-1), arrestin 4, neurofilament, CD117, CD44, Ki67, and cellular retinaldehyde-binding protein (CRALBP), followed by fluorescence and/or confocal microscopy examinations. Immunostaining of the tissue sections enabled clear observation of strongly GFAP-positive cells that corresponded to the inner-half layer of the foveolar Müller cell cone. The surface layer of the foveal slope was partially costained with GFAP and vimentin. Tuj-1-positive cells were observed in the innermost layer of the foveolar retina, which spanned to the surrounding ganglion cell layer. Moreover, colocalization of Tuj-1 and GFAP was observed at the foveal pit. The coexpression of CD117 and CD44 was found in the interphotoreceptor matrix of the fovea. The foveolar cone stained positive for both nestin and arrestin 4, however, the photoreceptor layer outside of the foveola displayed weak staining for nestin. Colocalization of nestin and vimentin was observed in the inner half of the Henle layer, while colocalization of nestin and neurofilament was observed in the outer half, predominantly. Scattered Ki67-positive cells were observed in the cellular processes of the outer plexiform layer and the ganglion cell layer around the foveola. Immunostaining for CRALBP was negative in most parts of the GFAP-positive area. The Müller cell cone was divided into GFAP-strongly positive cells, presumably astrocytes, in the inner layer and nestin-positive/GFAP-weakly positive radial glia-like cells in the outer layer. These findings indicated that groups of such undifferentiated cells in the foveola might be involved in maintaining morphology and regeneration.

Optical coherence tomographic features of macular telangiectasia type 2: Korean Macular Telangiectasia Type 2 Study—Report No. 1

“…The morphological and locational features of this inner retinal cavity on OCT images are consistent with the histologically known location of the Müller cell cone (MCC), and it is suggested that these cavities might be related to the MCC damage. The MCC is known to have no contact to synapses or neuronal elements other than the central cones and lateral process that extend to the deep capillary plexus at the border between the inner nuclear layer and the outer plexiform layer 6,7 . This could be the reason for the findings of the only inner retinal cyst without ELM disruption.…”

Spontaneous disappearance and recurrence of impending macular hole: a case report

“…It should be noted that it is difficult to attribute the improvement in VA and the restoration of the lamella structure of the fovea centralis simply to glial cell proliferation. In previous studies, we speculated the presence of neural stem cell-like cells with regenerative ability in the fovea centralis [15, 16], and reported the possible involvement of serine proteases such as chymase and tryptase in the vitreous body in the development of MH and ERM [17–19]. Since chymase has an apoptotic effect and tryptase induces tissue fibrosis, we theorized that such serine proteases might be involved in the pathogenesis of MH and ERM.…”

Involvement of the Retinal Pigment Epithelium in the Development of Retinal Lattice Degeneration

“…However, several recent studies have indicated that retinal stem cells capable of differentiating into neurons are present in the adult primate retina [ 36 , 37 , 38 , 39 ]. Müller and RPE cells, as well as retinal precursor cells in the foveola and peripheral retinal margin, have been considered as candidates of adult primate retinal stem cells [ 35 , 36 , 37 , 38 , 39 , 40 ]. In this study, we assumed that the retinal lattice degeneration might have been caused by the inhibition of the regenerative potential of retinal stem cells, possibly transdifferentiated RPE cells.…”