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Akina Hoshino, Chi Zhang, Rachel O Wong, Thomas Reh; Characterization of human fetal inner retinal development. Invest. Ophthalmol. Vis. Sci. 2016;57(12):1784.
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© ARVO (1962-2015); The Authors (2016-present)
Previous studies of the human fovea have focused primarily on the photoreceptors and opsin expression with limited investigation of inner retinal development. To better understand the development of the human inner retina, we characterized the temporal and spatial expression patterns of inner retinal neuronal and glial markers, in the fovea vs. the periphery.
Fixed human fetal retinas from 73-150 days (d) post-conception were sectioned and immunostained for markers of photoreceptors (OTX2, Recoverin, S-opsin, NR2E3), inner retinal neurons (CHX10/VSX2, OTX2, Recoverin, ONECUT-2, PROX1, HuC/D, Calbindin) and Muller glia (SOX2, SOX9, CRALBP). In the younger tissue samples, the fovea was identified as the area where the onset of a subset of gene expression preceded that of the periphery. At later stages, we defined the fovea as the area containing an outer nuclear layer consisting of a single layer of S-Opsin and NR2E3 negative photoreceptors; this distinctive S-cone and rod-free zone was detected as early as 96d.
Horizontal cells were present as early as we examined, at 73 days, throughout the retina, and by 110d they formed a single layer in the fovea. The first bipolar cells were detected in the fovea at 96d, and by 110d, the foveal bipolar cells had axonal arborizations in the inner plexiform layer. Also by 110d, all the major cell types of the fovea were present: cones, horizontal cells, bipolar cells, amacrine cells, ganglion cells, and Muller glia were all organized into appropriate lamina. We also found evidence for synaptic connections at this age, and found VGluT1 immunoreactivity in the inner and outer plexiform layers. Despite the relative maturity of the foveal region, areas outside of the fovea retained immature developmental features.
These studies demonstrate that the fovea is detectable as early as 96d in a human fetal retina, and this region completes neurogenesis as much as 50 days ahead of more peripheral regions of the retina. Further, our results show that by 110d, the late-generated cell types, the bipolar cells and Muller glia, have already begun their differentiation.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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