Neurogenesis and Specification of Retinal Ganglion Cells

Nguyen-Ba-Charvet, Kim T.; Rebsam, Alexandra

doi:10.3390/ijms21020451

Cited by 37 publications

(31 citation statements)

References 215 publications

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“…Neuropeptides also play an important role in development, and amacrine cells (ACs) are the major neuropeptide-secreting cells (Bagnoli et al, 2003). Sixty-three different types of ACs have been discovered (Nguyen-Ba-Charvet and Rebsam, 2020), and with the development of technology, new types of ACs are being confirmed. The ACs regulate the development and diseases of the retina via cell-cell interactions or neurotransmitter secretions (Masland, 2012).…”

Section: Introductionmentioning

confidence: 99%

Trilogy Development of Proopiomelanocortin Neurons From Embryonic to Adult Stages in the Mice Retina

Zhang

Wang

et al. 2021

Front. Cell Dev. Biol.

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Proopiomelanocortin-positive amacrine cells (POMC ACs) were first discovered in adult mouse retinas in 2010; however, the development of POMC-ACs has not been studied. We bred POMC-EGFP mice to label POMC-positive cells and investigated the development of POMC neurons from embryonic to adult stages. We found that POMC neuron development is mainly divided into three stages: the embryonic stage, the closed-eye stage, and the open-eye stage. Each stage has unique characteristics. In the embryonic stage, POMC neurons appeared in the retina at about E13. There was a cell number developmental peak at E15, followed by a steep decline at E16. POMC neurons showed a large soma and increased spine numbers at the closed-eye stage, and two dendritic sublaminas formed in the inner plexiform layer (IPL). The appearance and increased soma size and dendrite numbers did not occur continuously in space. We found that the soma number was asymmetric between the superior and inferior retinas according to the developmental topographic map. Density peaked in the superior retina, which existed persistently in the retinal ganglion cell layer (GCL), but disappeared from the inner nuclear layer (INL) at about P6. At the same time, the soma distribution in the INL was the most regular. At the open-eye stage, the development of POMC neurons was nearly stable only with only an increase in the IPL width, which increased the soma–dendrite distance.

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Section: Introductionmentioning

confidence: 99%

Trilogy Development of Proopiomelanocortin Neurons From Embryonic to Adult Stages in the Mice Retina

Zhang

Wang

et al. 2021

Front. Cell Dev. Biol.

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“…As this in vitro stem cell culture method mirrors normal retinal development, rod photoreceptors greatly outnumber the RGC-like cells produced, as naturally occurs in the mouse and human retina [ 18 , 19 ]. Indeed, the average yield of stem cell-derived RGC-like cells has been estimated to be between 0.1% and 30% of the total number of cells [ 15 , 20 , 21 , 22 , 23 , 24 ], similar to the normal percentage of RGCs in the retina at different developmental stages [ 25 , 26 , 27 ]. Additionally, the number of RGC-like cells decreases over time in 3D cultures [ 28 , 29 ].…”

Section: Introductionmentioning

confidence: 99%

Effects of Adult Müller Cells and Their Conditioned Media on the Survival of Stem Cell-Derived Retinal Ganglion Cells

Pereiro

Miltner

Torre

et al. 2020

Cells

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Retinal neurons, particularly retinal ganglion cells (RGCs), are susceptible to the degenerative damage caused by different inherited conditions and environmental insults, leading to irreversible vision loss and, ultimately, blindness. Numerous strategies are being tested in different models of degeneration to restore vision and, in recent years, stem cell technologies have offered novel avenues to obtain donor cells for replacement therapies. To date, stem cell–based transplantation in the retina has been attempted as treatment for photoreceptor degeneration, but the same tools could potentially be applied to other retinal cell types, including RGCs. However, RGC-like cells are not an abundant cell type in stem cell–derived cultures and, often, these cells degenerate over time in vitro. To overcome this limitation, we have taken advantage of the neuroprotective properties of Müller glia (one of the main glial cell types in the retina) and we have examined whether Müller glia and the factors they secrete could promote RGC-like cell survival in organoid cultures. Accordingly, stem cell-derived RGC-like cells were co-cultured with adult Müller cells or Müller cell-conditioned media was added to the cultures. Remarkably, RGC-like cell survival was substantially enhanced in both culture conditions, and we also observed a significant increase in their neurite length. Interestingly, Atoh7, a transcription factor required for RGC development, was up-regulated in stem cell-derived organoids exposed to conditioned media, suggesting that Müller cells may also enhance the survival of retinal progenitors and/or postmitotic precursor cells. In conclusion, Müller cells and the factors they release promote organoid-derived RGC-like cell survival, neuritogenesis, and possibly neuronal maturation.

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“…Retinal ganglion cells are the first cell type to be generated during retinogenesis ( Sidman, 1961 ; Rapaport et al, 2004 ). In the mouse, their birth begins around E11, peaks during mid-gestation while newborn retinal ganglion cells migrate to the ganglion cell layer (GCL) ( Drager, 1985 ; Young, 1985 ; Nguyen-Ba-Charvet and Rebsam, 2020 ). The detection of PCNA-negative apoptotic cells in Rint1 -deficient retinas may be explained by the loss of PCNA in dying progenitors or by the apoptosis of postmitotic cells after RINT1 loss.…”

Section: Resultsmentioning

confidence: 99%

RINT1 Loss Impairs Retinogenesis Through TRP53-Mediated Apoptosis

Gomes

Matos-Rodrigues

Frappart

et al. 2020

Front. Cell Dev. Biol.

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Genomic instability in the central nervous system (CNS) is associated with defective neurodevelopment and neurodegeneration. Congenital human syndromes that affect the CNS development originate from mutations in genes of the DNA damage response (DDR) pathways. RINT1 (Rad50-interacting protein 1) is a partner of RAD50, that participates in the cellular responses to DNA double-strand breaks (DSB). Recently, we showed that Rint1 regulates cell survival in the developing brain and its loss led to premature lethality associated with genomic stability. To bypass the lethality of Rint1 inactivation in the embryonic brain and better understand the roles of RINT1 in CNS development, we conditionally inactivated Rint1 in retinal progenitor cells (RPCs) during embryogenesis. Rint1 loss led to accumulation of endogenous DNA damage, but RINT1 was not necessary for the cell cycle checkpoint activation in these neural progenitor cells. As a consequence, proliferating progenitors and postmitotic neurons underwent apoptosis causing defective neurogenesis of retinal ganglion cells, malformation of the optic nerve and blindness. Notably, inactivation of Trp53 prevented apoptosis of the RPCs and rescued the generation of retinal neurons and vision loss. Together, these results revealed an essential role for TRP53-mediated apoptosis in the malformations of the visual system caused by RINT1 loss and suggests that defective responses to DNA damage drive retinal malformations.

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Neurogenesis and Specification of Retinal Ganglion Cells

Cited by 37 publications

References 215 publications

Trilogy Development of Proopiomelanocortin Neurons From Embryonic to Adult Stages in the Mice Retina

Trilogy Development of Proopiomelanocortin Neurons From Embryonic to Adult Stages in the Mice Retina

Effects of Adult Müller Cells and Their Conditioned Media on the Survival of Stem Cell-Derived Retinal Ganglion Cells

RINT1 Loss Impairs Retinogenesis Through TRP53-Mediated Apoptosis

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