Abstract
Retinal ganglion cells (RGCs) play important roles in retinogenesis. They are required for normal retinal histogenesis and retinal cell number balance. Developmental RGC loss is typically characterized by initial retinal neuronal number imbalance and subsequent loss of retinal neurons. However, it is not clear whether loss of a specific non-RGC cell type in the RGC-depleted retina is due to reduced cell production or subsequent degeneration. Taking advantage of three knockout mice with varying degrees of RGC depletion, we re-examined bipolar cell production in these retinas from various aspects. Results show that generation of the cone bipolar cells is correlated with the existing number of RGCs. However, generation of the rod bipolar cells is unaffected by RGC shortage. Results report the first observation that RGCs selectively influence the genesis of subsequent retinal cell types.
Highlights
The mammalian retina contains six major neuronal and one glial cell types
Other studies reported that rod bipolar cell (R-BPC) are significantly reduced in the Atoh72/2 retina suggesting either Atoh7 or Retinal ganglion cells (RGCs) are required for normal R-BPC production [10,11]
Our results indicate that production of cone bipolar cells (C-BPCs) is related to the existing number of RGCs, but production of R-BPC is independent from RGCs
Summary
The mammalian retina contains six major neuronal and one glial cell types. Among them, retinal ganglion cells (RGC), horizontal cells, amacrine cells and cone photoreceptors are born in the early phase of retinal neurogenesis and are regarded as embryonic or early cell types. RGC’s histogenic role is further supported by a transcriptome screening effort in Atoh72/2 retinas that have 95% developmental RGC loss, in which expression of Gli, a downstream effector to SHH signaling, is significantly reduced at stages of early retinal neurogenesis [7]. It is not known whether all subsequent retinal cell types rely on RGCs. Our earlier studies on the Atoh72/2 retina, which had only 5% of normal RGC number, showed unchanged rod bipolar cell (R-BPC) numbers implying production of R-BPCs is not affected in an RGC-depleted retina [8,9]. Our results indicate that production of C-BPC is related to the existing number of RGCs, but production of R-BPC is independent from RGCs
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