Retinal ganglion cells projecting to the accessory optic system in optokinetic blind albinotic rats are direction‐selective

Krause, Martin; Distler, C.; Hoffmann, Klaus‐Peter

doi:10.1111/ejn.12572

Cited by 7 publications

(8 citation statements)

References 46 publications

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“…In reptiles, amphibians and birds, only dRGCs project into the MTN, whereas in mammals only oRGCs have been reported as projecting into the MTN (Fite et al, 1981;Krause et al, 2014). Our results obtained from anterograde labeling clearly demonstrated a large increase in ipsilateral MTN projections in absence of Gsk3b, whereas it was absent or very dim in control animals.…”

Section: Discussionsupporting

confidence: 43%

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

Kisseleff

Vigouroux

Hottin

et al. 2021

Preprint

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Glycogen Synthase Kinase 3 (GSK) proteins (GSK3α and GSK3β) are key mediators of signaling pathways, with crucial roles in coordinating fundamental biological processes during neural development. Here we show that the complete loss of GSK3 signaling in mouse retinal progenitors leads to microphthalmia with broad morphological defects. Both proliferation of retinal progenitors and neuronal differentiation are impaired and result in enhanced cell death. A single wild-type allele of either Gsk3α or Gsk3β is able to rescue these phenotypes. In this genetic context, all cell types are present with a functional retina. However, we unexpectedly detect a large number of cells in the inner nuclear layer expressing retinal ganglion cell (RGC)-specific markers (called displaced RGCs, dRGCs) when at least one allele of Gsk3α is expressed. Excess dRGCs lead to increased number of axons projecting into the ipsilateral medial terminal nucleus, an area of the brain belonging to the non-image-forming visual circuit and poorly targeted by RGCs in wild-type retina. Transcriptome analysis and optomotor response assay suggest that at least a subset of dRGCs in Gsk3 mutant mice are direction-selective RGCs. Our study thus uncovers a unique role of GSK3 in controlling the genesis of dRGCs, a rare and poorly characterized retinal cell type.

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Section: Discussionsupporting

confidence: 43%

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

Kisseleff

Vigouroux

Hottin

et al. 2021

Preprint

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“…Smooth pursuit is driven by a small visual stimulus, such as a bird in flight, enabling the observer to see the object in greater detail, whereas the OKR responds to larger stimulus across the whole retina, such as the observation of telephone poles whilst on a moving train (Schraa-Tam et al, 2009). The OKR comprises eye movements that reduce and stabilize the movement of an image across the retina (called the retinal slip) in a compensatory fashion (Ackert et al, 2009; Cahill and Nathans, 2008; Hung et al, 2013; Iwashita et al, 2001; Katoh et al, 2005; Krause et al, 2014; Stahl, 2004; Sugita et al, 2013; Thomas et al, 2010; van Alphen and De Zeeuw, 2002; Yonehara et al, 2009). Retinal slip identified as the difference between the velocities of the image movement and of the eye’s corresponding tracking behavior, is detected by a distinct class of RGCs called direction-selective (DS) RGCs (Ackert et al, 2009).…”

Section: Behavioral Assays Measuring Deficits In Rodent Visual Promentioning

confidence: 99%

“…The AOS converts the retinal signal to a rotation estimate of the moving stimuli (Spoida et al, 2012; Stahl, 2004; Yonehara et al, 2009). In animals without a fovea, the DS-RGCs are particularly important in providing directional information to the AOS system, and are ultimately responsible for generating the OKR (Krause et al, 2014; Sugita et al, 2013). This reflex is elicited when the environment is in motion and drifts across the retina, which results in the eyes beginning to follow the visual stimulus’ direction (Sugita et al, 2013).…”

Section: Behavioral Assays Measuring Deficits In Rodent Visual Promentioning

confidence: 99%

Psychophysical testing in rodent models of glaucomatous optic neuropathy

Grillo

Koulen

2015

Experimental Eye Research

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Processing of visual information begins in the retina, with photoreceptors converting light stimuli into neural signals. Ultimately, signals are transmitted to the brain through signaling networks formed by interneurons, namely bipolar, horizontal and amacrine cells providing input to retinal ganglion cells (RGCs), which form the optic nerve with their axons. As part of the chronic nature of glaucomatous optic neuropathy, the increasing and irreversible damage and ultimately loss of neurons, RGCs in particular, occurs following progressive damage to the optic nerve head (ONH), eventually resulting in visual impairment and visual field loss. There are two behavioral assays that are typically used to assess visual deficits in glaucoma rodent models, the visual water task and the optokinetic drum. The visual water task can assess an animal’s ability to distinguish grating patterns that are associated with an escape from water. The optokinetic drum relies on the optomotor response, a reflex turning of the head and neck in the direction of the visual stimuli, which usually consists of rotating black and white gratings. This reflex is a physiological response critical for keeping the image stable on the retina. Driven initially by the neuronal input from direction-selective RGCs, this reflex is comprised of a number of critical sensory and motor elements. In the presence of repeatable and defined stimuli, this reflex is extremely well suited to analyze subtle changes in the circuitry and performance of retinal neurons. Increasing the cycles of these alternating gratings per degree, or gradually reducing the contrast of the visual stimuli, threshold levels can be determined at which the animal is no longer tracking the stimuli, and thereby visual function of the animal can be determined non-invasively. Integrating these assays into an array of outcome measures that determine multiple aspects of visual function is a central goal in vision research and can be realized, for example, by the combination of measuring optomotor reflex function with electroretinograms (ERGs) and optical coherence tomography (OCT) of the retina. These structure-function correlations in vivo are urgently needed to identify disease mechanisms as potential new targets for drug development. Such a combination of the experimental assessment of the optokinetic reflex (OKN) or optomotor reflex (OMR) with other measures of retinal structure and function is especially valuable for research on GON. The chronic progression of the disease is characterized by a gradual decrease in function accompanied by a concomitant increase in structural damage to the retina, therefore the assessment of subtle changes is key to determining the success of novel intervention strategies.

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“…To our knowledge, such a high number of dRGCs has never been reported in a transgenic/mutant animal. A previous study hypothesized that dRGCs are misplaced in the INL due to an ontogenic aberration rather than representing an independent class of RGCs (Fite et al, 1981;Krause et al, 2014). Indeed, differential cell adhesion plays a key role in sorting and migration of retinal cells in their appropriate layers, especially for RGCs.…”

Section: Discussionmentioning

confidence: 99%

Glycogen Synthase Kinase 3 Regulates the Genesis of Displaced Retinal Ganglion Cells3

Kisseleff

Vigouroux²,

Hottin

et al. 2021

eNeuro

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Glycogen Synthase Kinase 3 (GSK) proteins (GSK3 and GSK3 ) are key mediators of signaling pathways, with crucial roles in coordinating fundamental biological processes during neural development. Here we show that the complete loss of GSK3 signaling in mouse retinal progenitors leads to microphthalmia with broad morphological defects. A single wild-type allele of either Gsk3 or Gsk3 is able to rescue this phenotype. In this genetic context, all cell types are present with a functional retina. However, we unexpectedly detect a large number of cells in the inner nuclear layer expressing retinal ganglion cell (RGC)-specific markers (called displaced RGCs, dRGCs) when at least one allele of Gsk3α is expressed. Excess dRGCs lead to increased number of axons projecting into the ipsilateral medial terminal nucleus, an area of the brain belonging to the non-image-forming visual circuit and poorly targeted by RGCs in wild-type retina. Transcriptome analysis and optomotor response assay suggest that at least a subset of dRGCs in Gsk3 mutant mice are direction-selective RGCs. Our study thus uncovers a unique role of GSK3 in controlling the production of ganglion cells in the inner nuclear layer, which correspond to dRGCs, a rare and poorly characterized retinal cell type. Significance StatementGlycogen Synthase Kinase 3 (GSK) proteins (Gsk3 or Gsk3 ) are key mediators of signaling pathways, especially in the central nervous system but poorly described in the retina. Here we show that the complete loss of GSK3 in mouse retinal progenitors leads to microphthalmia. However, when only one allele of Gsk3 or Gsk3 are present, all cell types are present with a functional retina. More importantly, we unexpectedly uncover a unique role of GSK3 in controlling the genesis of retinal ganglion cells in the inner nuclear layer which could correspond to a rare and poorly characterized retinal cell type. Therefore, our mouse models potentially offer a unique and powerful model system to study the visual function of dRGCs in mammals.

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Retinal ganglion cells projecting to the accessory optic system in optokinetic blind albinotic rats are direction‐selective

Cited by 7 publications

References 46 publications

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

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

Psychophysical testing in rodent models of glaucomatous optic neuropathy

Glycogen Synthase Kinase 3 Regulates the Genesis of Displaced Retinal Ganglion Cells3

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