Glycogen Synthase Kinase 3 regulates the genesis of the rare displaced ganglion cell retinal subtype

Kisseleff, Elena; Vigouroux, Robin; Hottin, Catherine; Lourdel, Sopie; Shah, Palak; Chédotal, Alain; Perron, Muriel; Swaroop, Anand; Roger, Jérôme E.

doi:10.1101/2021.01.06.425300

Cited by 3 publications

(3 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, dRGCs also sharply concentrate in the same region slightly extending toward the temporal quadrant. In the mouse retina, dRGC neurogenesis is under the control of Glycogen Synthase Kinase 3 and may contribute to binocular vision as they project to the ipsilateral thalamus [ 72 , 73 ]. The functional role of dRGCs in TLGS remains to be explored.…”

Section: Discusionmentioning

confidence: 99%

Establishing the ground squirrel as a superb model for retinal ganglion cell disorders and optic neuropathies

Xiao

Zhao

Miyagishima

et al. 2021

Laboratory Investigation

View full text Add to dashboard Cite

Retinal ganglion cell (RGC) death occurs after optic nerve injury due to acute trauma or chronic degenerative conditions such as optic neuropathies (e.g. glaucoma). Currently, there are no effective therapies to prevent permanent vision loss resulting from RGC death, underlining the need for research on the pathogenesis of RGC disorders. Modeling human RGC/optic nerve diseases in non-human primates is ideal because of their similarity to humans, but has practical limitations including high cost and ethical considerations. In addition, many retinal degenerative disorders are age-related making the study in primate models prohibitively slow. For these reasons, mice and rats are commonly used to model RGC injuries. However, as nocturnal mammals, these rodents have retinal structures that differ from primates - possessing less than one-tenth of the RGCs found in the primate retina. Here we report the diurnal thirteen-lined ground squirrel (TLGS) as an alternative model. Compared to other rodent models, the number and distribution of RGCs in the TLGS retina are closer to primates. The TLGS retina possesses ~600,000 RGCs with the highest density along the equatorial retina matching the location of the highest cone density (visual streak). TLGS and primate retinas also share a similar interlocking pattern between RGC axons and astrocyte processes in the retina nerve fiber layer (RNFL). In addition, using TLGS we establish a new partial optic nerve injury model that precisely controls the extent of injury while sparing a portion of the retina as an ideal internal control for investigating the pathophysiology of axon degeneration and RGC death. Moreover, in vivo optical coherence tomography (OCT) imaging and ex vivo microscopic examinations of the retina in optic nerve injured TLGS confirm RGC loss precedes proximal axon degeneration, recapitulating human pathology. Thus, the TLGS retina is an excellent model, for translational research in neurodegeneration and therapeutic neuroprotection.

show abstract

Section: Discusionmentioning

confidence: 99%

Establishing the ground squirrel as a superb model for retinal ganglion cell disorders and optic neuropathies

Xiao

Zhao

Miyagishima

et al. 2021

Laboratory Investigation

View full text Add to dashboard Cite

show abstract

“…One interesting note is the possible mislocalization of cone cells bodies in the ONL as well as the presence of RBPMS + cells in the INL of the Chx10-Cre Lsd1 fl/fl mice. These cells may be displaced retinal ganglion cells, an extremely rare retinal subtype (Dräger and Olsen, 1981;Buhl and Dann, 1988;Doi et al, 1994;Nadal-Nicolás et al, 2014;Kisseleff et al, 2021); however, further validation via co-labeling of multiple antibodies and retrograde labeling beyond the scope of this present study are needed. We also investigated synaptic connections by co-labeling Bassoon and Ribeye, which are two components of the photoreceptors ribbon synapses (Brandstätter et al, 1999;Schmitz et al, 2000).…”

Section: Resultsmentioning

confidence: 84%

Deletion of histone demethylase Lsd1 (Kdm1a) during retinal development leads to defects in retinal function and structure

Ferdous

Shelton²,

Getz³

et al. 2023

Front. Cell. Neurosci.

View full text Add to dashboard Cite

PurposeThe purpose of this study was to investigate the role of Lysine specific demethylase 1 (Lsd1) in murine retinal development. LSD1 is a histone demethylase that can demethylate mono- and di-methyl groups on H3K4 and H3K9. Using Chx10-Cre and Rho-iCre75 driver lines, we generated novel transgenic mouse lines to delete Lsd1 in most retinal progenitor cells or specifically in rod photoreceptors. We hypothesize that Lsd1 deletion will cause global morphological and functional defects due to its importance in neuronal development.MethodsWe tested the retinal function of young adult mice by electroretinogram (ERG) and assessed retinal morphology by in vivo imaging by fundus photography and SD-OCT. Afterward, eyes were enucleated, fixed, and sectioned for subsequent hematoxylin and eosin (H&E) or immunofluorescence staining. Other eyes were plastic fixed and sectioned for electron microscopy.ResultsIn adult Chx10-Cre Lsd1fl/fl mice, we observed a marked reduction in a-, b-, and c-wave amplitudes in scotopic conditions compared to age-matched control mice. Photopic and flicker ERG waveforms were even more sharply reduced. Modest reductions in total retinal thickness and outer nuclear layer (ONL) thickness were observed in SD-OCT and H&E images. Lastly, electron microscopy revealed significantly shorter inner and outer segments and immunofluorescence showed modest reductions in specific cell type populations. We did not observe any obvious functional or morphological defects in the adult Rho-iCre75 Lsd1fl/fl animals.ConclusionLsd1 is necessary for neuronal development in the retina. Adult Chx10-Cre Lsd1fl/fl mice show impaired retinal function and morphology. These effects were fully manifested in young adults (P30), suggesting that Lsd1 affects early retinal development in mice.

show abstract

“…ERK signaling negatively regulates L-Maf, an important factor needed to promote the differentiation of lens cells from the neural retina [53]. GSK-3 plays an important role in neural and retinal development [54,55] and is also involved with a variety of other signaling pathways (Wnt, hedgehog, insulin and notch) [56][57][58][59]. Inhibited by Akt during non-canonical signaling, Marchena et al also found that inhibition of GSK-3 by treatment with small molecule inhibitors led to retinal cell neuroprotection in a retinitis pigmentosa model [60].…”

Section: Tgf-β/bmp Signaling: Neural and Retinal Developmentmentioning

confidence: 99%

The Role of Small Molecules and Their Effect on the Molecular Mechanisms of Early Retinal Organoid Development

Wagstaff

Berzal

Boon

et al. 2021

IJMS

View full text Add to dashboard Cite

Early in vivo embryonic retinal development is a well-documented and evolutionary conserved process. The specification towards eye development is temporally controlled by consecutive activation or inhibition of multiple key signaling pathways, such as the Wnt and hedgehog signaling pathways. Recently, with the use of retinal organoids, researchers aim to manipulate these pathways to achieve better human representative models for retinal development and disease. To achieve this, a plethora of different small molecules and signaling factors have been used at various time points and concentrations in retinal organoid differentiations, with varying success. Additions differ from protocol to protocol, but their usefulness or efficiency has not yet been systematically reviewed. Interestingly, many of these small molecules affect the same and/or multiple pathways, leading to reduced reproducibility and high variability between studies. In this review, we make an inventory of the key signaling pathways involved in early retinogenesis and their effect on the development of the early retina in vitro. Further, we provide a comprehensive overview of the small molecules and signaling factors that are added to retinal organoid differentiation protocols, documenting the molecular and functional effects of these additions. Lastly, we comparatively evaluate several of these factors using our established retinal organoid methodology.

show abstract

Glycogen Synthase Kinase 3 regulates the genesis of the rare displaced ganglion cell retinal subtype

Cited by 3 publications

References 63 publications

Establishing the ground squirrel as a superb model for retinal ganglion cell disorders and optic neuropathies

Establishing the ground squirrel as a superb model for retinal ganglion cell disorders and optic neuropathies

Deletion of histone demethylase Lsd1 (Kdm1a) during retinal development leads to defects in retinal function and structure

The Role of Small Molecules and Their Effect on the Molecular Mechanisms of Early Retinal Organoid Development

Contact Info

Product

Resources

About