scholarly journals The m6A reader YTHDF2 is a negative regulator for dendrite development and maintenance of retinal ganglion cells

2021 ◽  
Author(s):  
Fugui Niu ◽  
Peng Han ◽  
Jian Zhang ◽  
Yuanchu She ◽  
Lixin Yang ◽  
...  
Keyword(s):  
Visual Acuity ◽  
Ganglion Cells ◽  
Plexiform Layer ◽  
Conditional Knockout ◽  
Negative Regulator ◽  
Inner Plexiform Layer ◽  
Retinal Ganglion ◽  
Dendrite Branching ◽  
Target Mrnas ◽  
Dendrite Development

AbstractThe precise control of growth and maintenance of the retinal ganglion cell (RGC) dendrite arborization is critical for normal visual functions in mammals. However, the underlying mechanisms remain elusive. Here we find that the m6A reader YTHDF2 is highly expressed in the mouse RGCs. Conditional knockout (cKO) of Ythdf2 in the retina leads to increased RGC dendrite branching, resulting in more synapses in the inner plexiform layer. Interestingly, the Ythdf2 cKO mice show improved visual acuity compared with control mice. We further demonstrate that Ythdf2 cKO in the retina protects RGCs from dendrite degeneration caused by the experimental acute glaucoma model. We identify the m6A-modified YTHDF2 target transcripts which mediate these effects. This study reveals mechanisms by which YTHDF2 restricts RGC dendrite development and maintenance. YTHDF2 and its target mRNAs might be valuable in developing new treatment approaches for glaucomatous eyes.Impact statementThe m6A reader YTHDF2 negatively regulates RGC dendrite branching through destabilizing its m6A-modified target mRNAs encoding proteins controlling dendrite development and maintenance. Ythdf2 cKO improves visual acuity and alleviates acute ocular hypertension-induced glaucoma in mice.

Development of cholinergic amacrine cell stratification in the ferret retina and the effects of early excitotoxic ablation

2001 ◽  
Vol 18 (4) ◽  
pp. 559-570 ◽  
Author(s):  
B.E. REESE ◽  
M.A. RAVEN ◽  
K.A. GIANNOTTI ◽  
P.T. JOHNSON
Keyword(s):  
Ganglion Cell ◽  
Ganglion Cells ◽  
Plexiform Layer ◽  
Amacrine Cells ◽  
Cell Types ◽  
Retinal Cell ◽  
Inner Plexiform Layer ◽  
Retinal Ganglion ◽  
Outer Border ◽  
Cholinergic Amacrine Cells

The present study has examined the emergence of cholinergic stratification within the developing inner plexiform layer (IPL), and the effect of ablating the cholinergic amacrine cells on the formation of other stratifications within the IPL. The population of cholinergic amacrine cells in the ferret's retina was identified as early as the day of birth, but their processes did not form discrete strata until the end of the first postnatal week. As development proceeded over the next five postnatal weeks, so the positioning of the cholinergic strata shifted within the IPL toward the outer border, indicative of the greater ingrowth and elaboration of processes within the innermost parts of the IPL. To examine whether these cholinergic strata play an instructive role upon the development of other stratifications which form within the IPL, one-week-old ferrets were treated with l-glutamate in an attempt to ablate the population of cholinergic amacrine cells. Such treatment was shown to be successful, eliminating all of the cholinergic amacrine cells as well as the alpha retinal ganglion cells in the central retina. The remaining ganglion cell classes as well as a few other retinal cell types were partially reduced, while other cell types were not affected, and neither retinal histology nor areal growth was compromised in these ferrets. Despite this early loss of the cholinergic amacrine cells, which are eliminated within 24 h, other stratifications within the IPL formed normally, as they do following early elimination of the entire ganglion cell population. While these cholinergic amacrine cells are present well before other cell types have differentiated, apparently neither they, nor the ganglion cells, play a role in determining the depth of stratification for other retinal cell types.

The structural and functional development of the retina in larval Xenopus

Development ◽  
1975 ◽  
Vol 33 (4) ◽  
pp. 915-940
Author(s):  
S. H. Chung ◽  
R. Victoria Stirling ◽  
R. M. Gaze
Keyword(s):  
Ganglion Cells ◽  
Single Layer ◽  
Plexiform Layer ◽  
Distinct Pattern ◽  
Inner Plexiform Layer ◽  
Retinal Ganglion ◽  
Response Characteristics ◽  
Functional Development ◽  
New Type ◽  
Plexiform Layers

The structural transformations of the larval Xenopus retina at successive stages of development, and concomitant changes in response characteristics of retinal ganglion cells, were studied using histological and electrophysiological techniques. The first sign of visually evoked electrical responses appears at about the time when the ganglion cells spread out into a single layer and shortly after the inner and outer plexiform layers become discernible. Initially giving simple ‘on’ responses, the cells progressively change their response characteristics and become ‘event’ units. Subsequently, ‘dimming’ units can be identified. Throughout larval life, response properties of these two types become more distinct from one another and approximate to those found in the adult. So do the arborization patterns of the dendritic trees of the ganglion cells. Two types of branching patterns are identifiable in Golgi preparations. Around metamorphic climax, a new type of ganglion cell appears, coinciding with the emergence of ‘sustained’ units electrophysiologically. After metamorphosis, the retina still grows both in thickness (mainly in the inner plexiform layer) and diameter. The three unit types change such that they come to show pronounced inhibitory effects from the peripheral visual field on the receptive field and each unit type acquires a distinct pattern of endogenous discharge.

scholarly journals Temporal and mosaic distribution of large ganglion cells in the retina of a daggertooth aulopiform deep–sea fish ( Anotopterus pharao )

2000 ◽  
Vol 355 (1401) ◽  
pp. 1161-1166 ◽  
Author(s):  
M. Uemura ◽  
H. Somiya ◽  
M. Moku ◽  
K. Kawaguchi
Keyword(s):  
Ganglion Cells ◽  
Outer Part ◽  
Plexiform Layer ◽  
Inner Plexiform Layer ◽  
Retinal Ganglion ◽  
Cat Retina ◽  
Epipelagic Zone ◽  
Area Centralis ◽  
Mean Size ◽  
Mosaic Distribution

The daggertooth Anotopteruspharao (Aulopiformes: Anotopteridae) is a large, piscivorous predator that lives within the epipelagic zone at night. In this species, the distribution of retinal ganglion cells has been examined. An isodensity contour map of ganglion cells shows that the cells concentrate in a slightly ventral region of the temporal retina. The region of high ganglion cell density contains 4.07 × 10 3 cells mm −2 , and the resulting visual acuity is 3.5 cycles deg −1 . Outside the area centralis, conspicuously large ganglion cells (LGCs) are observed in the temporal margin of the retina. The LGCs are regularly arrayed, and displaced into the inner plexiform layer. Thick dendrites extend into the outer part (sublamina a) of the inner plexiform layer. In the retinal whole mount, the total number of LGCs is 1590 (90.7cm specimen), and the mean size of the LGCs is about four times larger than that of the ordinary ganglion cells. The morphological appearance of the LGCs was similar to the off–type alpha cells of the cat retina. The function of these distinctive LGCs is discussed in relation to specific head–up feeding behaviour.

scholarly journals Strip1 regulates retinal ganglion cell survival by suppressing Jun-mediated apoptosis to promote retinal neural circuit formation

2021 ◽  
Author(s):  
Mai Ahmed ◽  
Yutaka Kojima ◽  
Ichiro Masai
Keyword(s):  
Molecular Mechanisms ◽  
Neural Circuit ◽  
Ganglion Cells ◽  
Plexiform Layer ◽  
Bipolar Cells ◽  
Inner Plexiform Layer ◽  
Retinal Ganglion ◽  
Interacting Protein ◽  
Retina Development ◽  
Circuit Formation

In the vertebrate retina, an interplay between retinal ganglion cells (RGCs), amacrine and bipolar cells establishes a synaptic layer called the inner plexiform layer (IPL). This circuit conveys signals from photoreceptors to visual centers in the brain. However, the molecular mechanisms involved in its development remain poorly understood. Striatin-interacting protein 1 (Strip1) is a core component of the STRIPAK complex, and it has shown emerging roles in embryonic morphogenesis. Here, we uncover the importance of Strip1 in inner retina development. Using zebrafish, we show that loss of Strip1 causes defects in IPL formation. In strip1 mutants, RGCs undergo dramatic cell death shortly after birth. Amacrine and bipolar cells subsequently invade the degenerating RGC layer, leading to a disorganized IPL. Thus, Strip1 promotes IPL formation through RGC maintenance. Mechanistically, zebrafish Strip1 interacts with its STRIPAK partner, Striatin3, to promote RGC survival by suppressing Jun-mediated apoptosis. In addition to its function in RGC maintenance, Strip1 is required for RGC dendritic patterning, which likely contributes to proper IPL formation. Taken together, we propose that a series of Strip1-mediated regulatory events coordinates inner retinal circuit formation by maintaining RGCs during development, which ensures proper positioning and neurite patterning of inner retinal neurons.

Retinal ganglion cells projecting to the optic tectum and visual thalamus of lizards

2002 ◽  
Vol 19 (5) ◽  
pp. 575-581 ◽  
Author(s):  
ALINO MARTINEZ-MARCOS ◽  
ENRIQUE LANUZA ◽  
FERNANDO MARTINEZ-GARCIA
Keyword(s):  
Ganglion Cell ◽  
Retinal Ganglion Cells ◽  
Optic Tectum ◽  
Ganglion Cells ◽  
Plexiform Layer ◽  
Cell Types ◽  
Inner Plexiform Layer ◽  
Retinal Ganglion ◽  
Visual Thalamus ◽  
Podarcis Hispanica

Retinal ganglion cells projecting to the optic tectum and visual thalamus have been investigated in the lizard, Podarcis hispanica. Injections of biotinylated dextran-amine in the optic tectum reveal seven morphological cell varieties including one displaced ganglion cell type. Injections in the visual thalamus yield similar ganglion cell classes plus four giant ganglion cells, including two displaced ganglion cell types. The present study constitutes the first comparison of tectal versus thalamic ganglion cell types in reptiles. The situation found in lizards is similar to that reported in mammals and birds where some cell types projecting to the thalamus are larger than those projecting to the mesencephalic roof. The presence of giant retino-thalamic ganglion cells with specific dendritic arborizations in sublaminae A and B of the inner plexiform layer suggests that parts of the visual thalamus of lizards could be implicated in movement detection, a role that might be played by the ventral lateral geniculate nucleus, which is involved in our tracer injections.

Disruption of transient photoreceptor targeting within the inner plexiform layer following early ablation of cholinergic amacrine cells in the ferret

2001 ◽  
Vol 18 (5) ◽  
pp. 741-751 ◽  
Author(s):  
P.T. JOHNSON ◽  
M.A. RAVEN ◽  
B.E. REESE
Keyword(s):  
Retinal Ganglion Cells ◽  
Amacrine Cell ◽  
Ganglion Cells ◽  
Plexiform Layer ◽  
Amacrine Cells ◽  
Inner Plexiform Layer ◽  
Retinal Ganglion ◽  
Subcutaneous Injections ◽  
Cell Processes ◽  
Cholinergic Amacrine Cells

Photoreceptors in the ferret's retina have been shown to project transiently to the inner plexiform layer (IPL) prior to their differentiation of an outer segment. On postnatal day 15 (P-15), when this projection achieves maximal density, the photoreceptors projecting into the IPL extend primarily to one of two depths, coincident with the processes of cholinergic amacrine cells. The present study has used an excitotoxic approach employing subcutaneous injections of l-glutamate to ablate these cholinergic amacrine cells on P-7, in order to see whether their elimination alters this targeting of photoreceptor terminals within the IPL. The near-complete elimination of cholinergic amacrine cells at P-15 was confirmed, although the population of retinal ganglion cells was also affected, being depleted by roughly 50%. The rod opsin-immunopositive terminals in such treated ferrets no longer showed a stratified distribution, being found throughout the depth of the IPL, as well as extending into the ganglion cell layer. This effect should not be due to the partial loss of retinal ganglion cells, however, since optic nerve transection at P-2, which eliminates the ganglion cells entirely while leaving the cholinergic amacrine cell population intact, was shown not to affect the stratification pattern of the photoreceptors within the IPL. These results strongly suggest that the targeting of the photoreceptor terminals to discrete strata within the IPL is dependent upon the cholinergic amacrine cell processes.

scholarly journals Adeno-associated virus-RNAi of GlyRα1 and characterization of its synapse-specific inhibition in OFF alpha transient retinal ganglion cells

2014 ◽  
Vol 112 (12) ◽  
pp. 3125-3137 ◽  
Author(s):  
C. Zhang ◽  
S. B. Rompani ◽  
B. Roska ◽  
M. A. McCall
Keyword(s):  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Glutamate Release ◽  
Plexiform Layer ◽  
Resting Membrane Potential ◽  
Inner Plexiform Layer ◽  
Retinal Ganglion ◽  
Decay Kinetics ◽  
Adeno Associated Virus ◽  
Α Subunit

In the central nervous system, inhibition shapes neuronal excitation. In spinal cord glycinergic inhibition predominates, whereas GABAergic inhibition predominates in the brain. The retina uses GABA and glycine in approximately equal proportions. Glycinergic crossover inhibition, initiated in the On retinal pathway, controls glutamate release from presynaptic OFF cone bipolar cells (CBCs) and directly shapes temporal response properties of OFF retinal ganglion cells (RGCs). In the retina, four glycine receptor (GlyR) α-subunit isoforms are expressed in different sublaminae and their synaptic currents differ in decay kinetics. GlyRα1, expressed in both On and Off sublaminae of the inner plexiform layer, could be the glycinergic isoform that mediates On-to-Off crossover inhibition. However, subunit-selective glycine contributions remain unknown because we lack selective antagonists or cell class-specific subunit knockouts. To examine the role of GlyRα1 in direct inhibition in mature RGCs, we used retrogradely transported adeno-associated virus (AAV) that performed RNAi and eliminated almost all glycinergic spontaneous and visually evoked responses in PV5 (OFFαTransient) RGCs. Comparisons of responses in PV5 RGCs infected with AAV-scrambled-short hairpin RNA (shRNA) or AAV- Glra1-shRNA confirm a role for GlyRα1 in crossover inhibition in cone-driven circuits. Our results also define a role for direct GlyRα1 inhibition in setting the resting membrane potential of PV5 RGCs. The absence of GlyRα1 input unmasked a serial and a direct feedforward GABAAergic modulation in PV5 RGCs, reflecting a complex interaction between glycinergic and GABAAergic inhibition.

scholarly journals Retinal Ganglion Cell Atrophy in Homonymous Hemianopia due to Acquired Occipital Lesions Observed Using Cirrus High-Definition-OCT

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Tsutomu Yamashita ◽  
Atsushi Miki ◽  
Katsutoshi Goto ◽  
Syunsuke Araki ◽  
Go Takizawa ◽  
...  
Keyword(s):  
Ganglion Cell ◽  
Ganglion Cells ◽  
Plexiform Layer ◽  
Homonymous Hemianopia ◽  
Inner Plexiform Layer ◽  
Retinal Ganglion ◽  
High Definition ◽  
Fiber Layer ◽  
The Relationship ◽  
Negative Linear Relationship

Purpose. To report a reduction in macular ganglion cell layer and inner plexiform layer (GCL+IPL) thickness and circumpapillary retinal nerve fiber layer (cpRNFL) thickness using spectral-domain optical coherence tomography in patients with homonymous hemianopia due to posterior cerebral artery (PCA) stroke.Methods. Seven patients with PCA stroke were examined using Cirrus high-definition-OCT. The GCL+IPL thicknesses were divided into the hemianopic and unaffected sides. The relationship between the time after stroke and the GCL+IPL thicknesses in the hemianopic side was evaluated.Results. The average thicknesses of the GCL+IPL were 64.6 and 82.0 μm on the hemianopic and unaffected sides, respectively, and the measurement was significantly thinner on the former side (p=0.018). A regression analysis revealed a negative linear relationship (R2=0.574,p=0.049) between the time after stoke and the GCL+IPL thicknesses on the hemianopic side. The supratemporal and inferotemporal cpRNFL thicknesses in the eyes ipsilateral to the stroke showed a significant reduction.Conclusion. Our findings confirmed our previous observations that the degeneration of retinal ganglion cells can occur after PCA stroke. GCL+IPL thinning was demonstrated in the hemiretinae corresponding to the affected hemifields. Also, it is suggested that the retinal changes observed are progressive.

scholarly journals Recurrent axon collaterals of intrinsically photosensitive retinal ganglion cells

2013 ◽  
Vol 30 (4) ◽  
pp. 175-182 ◽  
Author(s):  
HANNAH R. JOO ◽  
BETH B. PETERSON ◽  
DENNIS M. DACEY ◽  
SAMER HATTAR ◽  
SHIH-KUO CHEN
Keyword(s):  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Plexiform Layer ◽  
Small Subset ◽  
Inner Plexiform Layer ◽  
Retinal Ganglion ◽  
Light Responses ◽  
Genetic Method ◽  
Axon Collaterals ◽  
The Brain

AbstractRetinal ganglion cells (RGCs), the output neurons of the retina, have axons that project via the optic nerve to diverse targets in the brain. Typically, RGC axons do not branch before exiting the retina and thus do not provide it with synaptic feedback. Although a small subset of RGCs with intraretinal axon collaterals has been previously observed in human, monkey, cat, and turtle, their function remains unknown. A small, more recently identified population of RGCs expresses the photopigment melanopsin. These intrinsically photosensitive retinal ganglion cells (ipRGCs) transmit an irradiance-coding signal to visual nuclei in the brain, contributing both to image-forming vision and to several nonimage-forming functions, including circadian photoentrainment and the pupillary light reflex. In this study, using melanopsin immunolabeling in monkey and a genetic method to sparsely label the melanopsin cells in mouse, we show that a subgroup of ipRGCs have axons that branch en route to the optic disc, forming intraretinal axon collaterals that terminate in the inner plexiform layer of the retina. The previously described collateral-bearing population identified by intracellular dye injection is anatomically indistinguishable from the collateral-bearing melanopsin cells identified here, suggesting they are a subset of the melanopsin-expressing RGC type and may therefore share its functional properties. Identification of an anatomically distinct subpopulation in mouse, monkey, and human suggests this pathway may be conserved in these and other species (turtle and cat) with intraretinal axon collaterals. We speculate that ipRGC axon collaterals constitute a likely synaptic pathway for feedback of an irradiance signal to modulate retinal light responses.

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