PDGF and its receptors in the developing rodent retina and optic nerve

Development ◽  
1993 ◽  
Vol 118 (2) ◽  
pp. 539-552 ◽  
Author(s):  
H.S. Mudhar ◽  
R.A. Pollock ◽  
C. Wang ◽  
C.D. Stiles ◽  
W.D. Richardson
Keyword(s):  
Optic Nerve ◽  
Optic Chiasm ◽  
Inner Nuclear Layer ◽  
Mouse Retina ◽  
Beta Subunits ◽  
Retinal Ganglion ◽  
Rna Transcripts ◽  
Eye Opening ◽  
Optic Fibre ◽  
Ganglion Neurons

We have used in situ hybridization to visualize cells in the developing rat retina and optic nerve that express mRNAs encoding the A and B chains of platelet-derived growth factor (PDGF-A and PDGF-B), and the alpha and beta subunits of the PDGF receptor (PDGF-alpha R and PDGF-beta R). We have also visualized PDGF-A protein in these tissues by immunohistochemistry. In the retina, PDGF-A mRNA is present in pigment epithelial cells, ganglion neurons and a subset of amacrine neurons. PDGF-A transcripts accumulate in ganglion neurons during target innervation and in amacrine neurons around the time of eye opening, suggesting that PDGF-A expression in these cells may be regulated by target-derived signals or by electrical activity. In the mouse retina, PDGF-A immunoreactivity is present in the cell bodies, dendrites and proximal axons of ganglion neurons, and throughout the inner nuclear layer. PDGF-alpha R mRNA is expressed in the retina by astrocytes in the optic fibre layer and by a subset of cells in the inner nuclear layer that might be Muller glia or bipolar neurons. Taken together, our data suggest short-range paracrine interactions between PDGF-A and PDGF-alpha R, the ligand and its receptor being expressed in neighbouring layers of cells in the retina. In the optic nerve, PDGF-A immunoreactivity is present in astrocytes but apparently not in the retinal ganglion cell axons. PDGF-alpha R+ cells in the optic nerve first appear near the optic chiasm and subsequently spread to the retinal end of the nerve; these PDGF-alpha R+ cells are probably oligodendrocyte precursors (Pringle et al., 1992). RNA transcripts encoding PDGF-B and PDGF-beta R are expressed by cells of the hyaloid and mature vascular systems in the eye and optic nerve.

scholarly journals Pan-Retinal Characterisation of Light Responses from Ganglion Cells in the Developing Mouse Retina

2016 ◽  
Author(s):  
Gerrit Hilgen ◽  
Sahar Pirmoradian ◽  
Daniela Pamplona ◽  
Pierre Kornprobst ◽  
Bruno Cessac ◽  
...  
Keyword(s):  
Large Scale ◽  
Ganglion Cells ◽  
Mouse Retina ◽  
Multielectrode Array ◽  
Retinal Ganglion ◽  
Developmental Profile ◽  
Light Responses ◽  
Ecological Requirements ◽  
Eye Opening ◽  
Dorsal Retina

AbstractWe have investigated the ontogeny of light-driven responses in mouse retinal ganglion cells (RGCs). Using a large-scale, high-density multielectrode array, we recorded from hundreds to thousands of RGCs simultaneously at pan-retinal level, including dorsal and ventral locations. Responses to different contrasts not only revealed a complex developmental profile for ON, OFF and ON-OFF RGC types, but also unveiled differences between dorsal and ventral RGCs. At eye-opening, dorsal RGCs of all types were more responsive to light, perhaps indicating an environmental priority to nest viewing for pre-weaning pups. The developmental profile of ON and OFF RGCs exhibited antagonistic behavior, with the strongest ON responses shortly after eye-opening, followed by an increase in the strength of OFF responses later on. Further, we found that with maturation receptive field (RF) center sizes decrease, responses to light get stronger, and centers become more circular while seeing differences in all of them between RGC types. These findings show that retinal functionality is not spatially homogeneous, likely reflecting ecological requirements that favour the early development of dorsal retina, and reflecting different roles in vision in the mature animal.

scholarly journals Slit2 is essential for correct retinal ganglion cell axon fasciculation and midline crossing in the zebrafish

2020 ◽  
Author(s):  
Camila Davison ◽  
Flavio R. Zolessi
Keyword(s):  
Optic Nerve ◽  
Ganglion Cell ◽  
Retinal Ganglion Cell ◽  
Ganglion Cells ◽  
Axon Growth ◽  
Amacrine Cells ◽  
Optic Chiasm ◽  
Retinal Ganglion ◽  
Functional Connection ◽  
Optic Nerves

ABSTRACTThe functional connection of the retina with the brain implies the extension of retinal ganglion cells axons through a long and tortuous path. Slit-Robo signaling has been implicated in axon growth and guidance in several steps of this journey. Here, we analyzed in detail the expression pattern of slit2 in zebrafish embryos by whole-mount fluorescent in situ hybridization, to extend previous work on this and other species. Major sites of expression are amacrine cells in the retina from 40 hpf, as well as earlier expression around the future optic nerve, anterior to the optic chiasm, two prominent cell groups in the anterior forebrain and the ventral midline of the caudal brain and spinal cord. To further characterize slit2 function in retinal axon growth and guidance, we generated and phenotypically characterized a null mutant for this gene, using CRISPR-Cas9 technology. Although no evident defects were found on intraretinal axon growth or in the formation of the optic tracts or tectal innervation, we observed very characteristic and robust impairment on axon fasciculation at the optic nerves and chiasm. The optic nerves appeared thicker and defasciculated only in maternal-zygotic mutants, while a very particular unilateral nerve-splitting phenotype was evident at the optic chiasm in a good proportion of both zygotic and maternal-zygotic mutants. Our results support the idea of a channeling role for Slit molecules in retinal ganglion cell axons at the optic nerve level, in addition to a function in the segregation of axons coming from each nerve at the optic chiasm.

scholarly journals When is a control not a control? Reactive microglia occur throughout the control contralateral visual pathway in experimental glaucoma

2019 ◽  
Author(s):  
James R Tribble ◽  
Eirini Kokkali ◽  
Amin Otmani ◽  
Flavia Plastino ◽  
Emma Lardner ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Animal Models ◽  
Ganglion Cell ◽  
Retinal Ganglion Cell ◽  
Internal Control ◽  
Visual Pathway ◽  
Optic Chiasm ◽  
Retinal Ganglion ◽  
Reactive Microglia ◽  
Contralateral Eye

AbstractPurposeAnimal models show retinal ganglion cell injuries that replicate features of glaucoma and the contralateral eye is commonly used as an internal control. There is significant cross-over of retinal ganglion cell axons from the ipsilateral to the contralateral side at the level of the optic chiasm which may confound findings when damage is restricted to one eye. The effect of unilateral glaucoma on neuroinflammatory damage to the contralateral visual pathway has largely been unexplored.MethodsOcular hypertensive glaucoma was induced unilaterally or bilaterally in the rat and retinal ganglion cell neurodegenerative events were assessed. Neuroinflammation was quantified in the retina, optic nerve head, optic nerve, lateral geniculate nucleus, and superior colliculus by high resolution imaging, and in the retina by flow cytometry and protein arrays.ResultsFollowing ocular hypertensive stress, peripheral monocytes enter the retina, and microglia become reactive. This effect is more marked in animals with bilateral ocular hypertensive glaucoma. In rats where glaucoma was induced unilaterally there was significant microglia activation in the contralateral (control) eye. Microglial activation extended into the optic nerve and terminal visual thalami, where it was similar across hemispheres irrespective of whether ocular hypertension was unilateral or bilateral.ConclusionsThese data suggest that caution is warranted when using the contralateral eye as control in unilateral models of glaucoma.Translational RelevanceUse of a contralateral eye as a control may confound discovery of human relevant mechanism and treatments in animal models. We also identify neuroinflammatory protein responses that warrant further investigation as potential disease modifiable targets.

scholarly journals Subtype-dependent postnatal development of direction- and orientation-selective retinal ganglion cells in mice

2014 ◽  
Vol 112 (9) ◽  
pp. 2092-2101 ◽  
Author(s):  
Hui Chen ◽  
Xiaorong Liu ◽  
Ning Tian
Keyword(s):  
Postnatal Development ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Light Response ◽  
Orientation Selectivity ◽  
Mouse Retina ◽  
Retinal Ganglion ◽  
Tuning Width ◽  
Eye Opening ◽  
Synaptic Mechanisms

The direction-selective ganglion cells (DSGCs) and orientation-selective ganglion cells (OSGCs) encode the directional and the orientational information of a moving object, respectively. It is unclear how DSGCs and OSGCs mature in the mouse retina during postnatal development. Here we investigated the development of DSGCs and OSGCs after eye-opening. We show that 1) DSGCs and OSGCs are present at postnatal day 12 (P12), just before eye-opening; 2) the fractions of both DSGCs and OSGCs increase from P12 to P30; 3) the development of DSGCs and OSGCs is subtype dependent; and 4) direction and orientation selectivity are two separate features of retinal ganglion cells (RGCs) in the mouse retina. We classified RGCs into different functional subtypes based on their light response properties. Compared with P12, the direction and orientation selectivity of ON-OFF RGCs but not ON RGCs became stronger at P30. The tuning width of DSGCs for both ON and ON-OFF subtypes decreased with age. For OSGCs, we divided them into non-direction-selective (non-DS) OSGCs and direction-selective OSGCs (DS&OSGCs). For DS&OSGCs, we found that there was no correlation between the direction and orientation selectivity, and that the tuning width of both ON and ON-OFF subtypes remained unchanged with age. For non-DS OSGCs, the tuning width of ON but not ON-OFF subtype decreased with development. These findings provide a foundation to reveal the molecular and synaptic mechanisms underlying the development of the direction and orientation selectivity in the retina.

The change of microglia numbers within the mice retina, optic nerve and chiasm following intravitreal AAV2-GFP injection

2021 ◽  
pp. 112067212110490
Author(s):  
Yuanfei Ji ◽  
Bo Yu ◽  
Yikui Zhang ◽  
Wencan Wu
Keyword(s):  
Optic Nerve ◽  
Intravitreal Injection ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Optic Chiasm ◽  
Optimal Concentration ◽  
The Other ◽  
Retinal Ganglion ◽  
Sparse Labeling ◽  
Microglial Morphology

Purpose To explore the optimized concentration of AAV2-GFP for sparse transfection of retinal ganglion cells (RGCs) and optic nerve (ON), and to examine the changes of microglial morphology and distribution in the retina, optic nerve and chiasm after injection. Methods We defined the optimal concentration of AAV2-GFP for sparse labeling of RGCs and axons in WT mice. We further explored the changes of microglial morphology and distribution in the retina, optic nerve and chiasm after intravitreal injection in CX3CR1+/GFP mice. Results 14 days after intravitreal injection of AAV2-GFP, live imaging of the retina showed that fundus fluorescence was very strong and dense at 2.16 × 1011 VG/retina, 2.16 × 1010 VG/retina, 2.16 × 109 VG/retina. RGCs were sparsely marked at a concentration 1:1000 (2.16 × 108 VG/retina) and fundus fluorescence was weak. The transfected RGCs and axons were unevenly distributed in the retina and significantly more RGCs were transfected near the injection site of AAV2-GFP compared to the other sites of the flat-mounted retina. Microglia density increased significantly in the retina and part of optic nerve, but not in the optic chiasm. The morphology of microglia was largely unchanged. Conclusions AAV2-GFP was highly efficient and the optimal concentration of sparsely labeled RGCs was 1:1000 (2.16 × 108 VG/retina). After intravitreal injection of AAV2-GFP, the number of microglia increased partly. The morphology of microglia was comparable.

scholarly journals Boosting CNS axon regeneration by harnessing antagonistic effects of GSK3 activity

2017 ◽  
Vol 114 (27) ◽  
pp. E5454-E5463 ◽  
Author(s):  
Marco Leibinger ◽  
Anastasia Andreadaki ◽  
Renate Golla ◽  
Evgeny Levin ◽  
Alexander M. Hilla ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Nerve Regeneration ◽  
Peripheral Nerves ◽  
Axon Regeneration ◽  
Growth Promotion ◽  
Peripheral Nerve Regeneration ◽  
Neurite Growth ◽  
Optic Chiasm ◽  
Retinal Ganglion ◽  
Optic Nerve Regeneration

Implications of GSK3 activity for axon regeneration are often inconsistent, if not controversial. Sustained GSK3 activity in GSK3S/A knock-in mice reportedly accelerates peripheral nerve regeneration via increased MAP1B phosphorylation and concomitantly reduces microtubule detyrosination. In contrast, the current study shows that lens injury-stimulated optic nerve regeneration was significantly compromised in these knock-in mice. Phosphorylation of MAP1B and CRMP2 was expectedly increased in retinal ganglion cell (RGC) axons upon enhanced GSK3 activity, but, surprisingly, no GSK3-mediated CRMP2 inhibition was detected in sciatic nerves, thus revealing a fundamental difference between central and peripheral axons. Conversely, genetic or shRNA-mediated conditional KO/knockdown of GSK3β reduced inhibitory phosphorylation of CRMP2 in RGCs and improved optic nerve regeneration. Accordingly, GSK3β KO-mediated neurite growth promotion and myelin disinhibition were abrogated by CRMP2 inhibition and largely mimicked in WT neurons upon expression of constitutively active CRMP2 (CRMP2T/A). These results underscore the prevalent requirement of active CRMP2 for optic nerve regeneration. Strikingly, expression of CRMP2T/A in GSK3S/A RGCs further boosted optic nerve regeneration, with axons reaching the optic chiasm within 3 wk. Thus, active GSK3 can also markedly promote axonal growth in central nerves if CRMP2 concurrently remains active. Similar to peripheral nerves, GSK3-mediated MAP1B phosphorylation/activation and the reduction of microtubule detyrosination contributed to this effect. Overall, these findings reconcile conflicting data on GSK3-mediated axon regeneration. In addition, the concept of complementary modulation of normally antagonistically targeted GSK3 substrates offers a therapeutically applicable approach to potentiate the regenerative outcome in the injured CNS.

A glial palisade delineates the ipsilateral optic projection in Monodelphis

1998 ◽  
Vol 15 (2) ◽  
pp. 397-400 ◽  
Author(s):  
ROBERT E. MacLAREN
Keyword(s):  
Optic Nerve ◽  
Axon Guidance ◽  
Turning Point ◽  
Linear Array ◽  
Ganglion Cells ◽  
Optic Tract ◽  
Optic Chiasm ◽  
Retinal Ganglion ◽  
Discrete Population ◽  
Distinct Morphology

In developing marsupials, the path taken through the optic chiasm by ipsilaterally projecting retinal ganglion cells is complicated. Just prior to entry into the chiasm, ganglion cells destined for the ipsilateral optic tract separate from the remainder of axons by turning abruptly downwards to take a position in the ventral part of the optic nerve. In this report, it is shown that a discrete population of about 10–15 large glial cells transiently form a linear array across the prechiasmatic part of the optic nerve, precisely at this axon turning point. The distinct morphology of these cells and their novel location may reflect a specialized role in axon guidance.

scholarly journals CD82 protects against glaucomatous axonal transport deficits via mTORC1 activation in mice

2021 ◽  
Vol 12 (12) ◽  
Author(s):  
Meng Ye ◽  
Jingqiu Huang ◽  
Qianxue Mou ◽  
Jing Luo ◽  
Yuanyuan Hu ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Axonal Transport ◽  
Cell Loss ◽  
Nerve Degeneration ◽  
Mouse Retina ◽  
Retinal Ganglion ◽  
Nerve Crush ◽  
Neuroprotective Strategy ◽  
Mtorc1 Activation

AbstractGlaucoma is a leading cause of irreversible blindness worldwide and is characterized by progressive optic nerve degeneration and retinal ganglion cell loss. Axonal transport deficits have been demonstrated to be the earliest crucial pathophysiological changes underlying axonal degeneration in glaucoma. Here, we explored the role of the tetraspanin superfamily member CD82 in an acute ocular hypertension model. We found a transient downregulation of CD82 after acute IOP elevation, with parallel emergence of axonal transport deficits. The overexpression of CD82 with an AAV2/9 vector in the mouse retina improved optic nerve axonal transport and ameliorated subsequent axon degeneration. Moreover, the CD82 overexpression stimulated optic nerve regeneration and restored vision in a mouse optic nerve crush model. CD82 exerted a protective effect through the upregulation of TRAF2, which is an E3 ubiquitin ligase, and activated mTORC1 through K63-linked ubiquitylation and intracellular repositioning of Raptor. Therefore, our study offers deeper insight into the tetraspanin superfamily and demonstrates a potential neuroprotective strategy in glaucoma treatment.

Sign in / Sign up

Export Citation Format

Share Document