scholarly journals Differential susceptibility of retinal ganglion cell subtypes in acute and chronic models of injury and disease

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Kirstin B. VanderWall ◽  
Bin Lu ◽  
Jorge S. Alfaro ◽  
Anna R. Allsop ◽  
Alexa S. Carr ◽  
...  
Keyword(s):  
Visual Information ◽  
Ganglion Cells ◽  
Differential Susceptibility ◽  
Retinal Ganglion ◽  
Nerve Crush ◽  
Disease Response ◽  
Models Of Injury ◽  
Main Cell Type ◽  
The Brain ◽  
Glial Reactivity

Abstract Retinal ganglion cells (RGCs) are a heterogeneous population of neurons, comprised of numerous subtypes that work synchronously to transmit visual information to the brain. In blinding disorders such as glaucoma, RGCs are the main cell type to degenerate and lead to loss of vision. Previous studies have identified and characterized a variety of RGC subtypes in animal models, although only a handful of studies demonstrate the differential loss of these RGC subtypes in response to disease or injury. Thus, efforts of the current study utilized both chronic (bead occlusion) and acute (optic nerve crush, ONC) rat models to characterize disease response and differential loss of RGC subtypes. Bead occlusion and ONC retinas demonstrated significant RGC loss, glial reactivity and apoptosis compared to control retinas. Importantly, bead occlusion and ONC retinas resulted in differential subtype-specific loss of RGCs, with a high susceptibility for alpha- and direction selective-RGCs and preferential survival of ipRGCs. Results of this study serve as an important foundation for future experiments focused on the mechanisms resulting in the loss of RGCs in optic neuropathies, as well as the development of targeted therapeutics for RGC subtype-specific neuroprotection.

scholarly journals Differential Susceptibility of Rat Retinal Ganglion Cells Following Optic Nerve Crush

2018 ◽  
Author(s):  
Kirstin B. VanderWall ◽  
Bin Lu ◽  
Shaomei Wang ◽  
Jason S. Meyer
Keyword(s):  
Optic Nerve ◽  
Retinal Ganglion Cells ◽  
Visual Information ◽  
Ganglion Cells ◽  
Differential Susceptibility ◽  
Optic Nerve Crush ◽  
Retinal Ganglion ◽  
Nerve Crush ◽  
Main Cell Type ◽  
Eventual Loss

AbstractRetinal ganglion cells (RGCs) are a heterogeneous group of cells, comprised of numerous subpopulations, that work together to send visual information to the brain. In numerous blinding disorders termed optic neuropathies, RGCs are the main cell type affected leading to degeneration of these cells and eventual loss of vision. Previous studies have identified and characterized RGC subtypes in numerous animal systems, with only a handful of studies demonstrating their differential loss in response to disease and injury. Thus, efforts of the current study utilized an optic nerve crush (ONC) model to characterize the loss of RGCs and disease phenotypes associated with this injury. Additionally, the loss of RGC subtypes including direction selective-, alpha-, and ip-RGCs following ONC was explored. Results of this study demonstrated the differential loss of RGC subtypes with a high susceptibility for loss of alpha- and direction selective-RGCs and the preferential survival of ip-RGCs following ONC and allows for the establishment of additional studies focused on mechanisms and loss of these cells in optic neuropathies. Additionally, these results put important emphasis on the development of therapeutics targeted at the loss of specific subtypes as well as cellular replacement following injury and disease.

scholarly journals A method for single-neuron chronic recording from the retina in awake mice

Science ◽  
2018 ◽  
Vol 360 (6396) ◽  
pp. 1447-1451 ◽  
Author(s):  
Guosong Hong ◽  
Tian-Ming Fu ◽  
Mu Qiao ◽  
Robert D. Viveros ◽  
Xiao Yang ◽  
...  
Keyword(s):  
Retinal Ganglion Cells ◽  
Visual Information ◽  
Single Neuron ◽  
Ganglion Cells ◽  
Ex Vivo ◽  
Neural Circuitry ◽  
Retinal Ganglion ◽  
Chronic Recording ◽  
The Brain

The retina, which processes visual information and sends it to the brain, is an excellent model for studying neural circuitry. It has been probed extensively ex vivo but has been refractory to chronic in vivo electrophysiology. We report a nonsurgical method to achieve chronically stable in vivo recordings from single retinal ganglion cells (RGCs) in awake mice. We developed a noncoaxial intravitreal injection scheme in which injected mesh electronics unrolls inside the eye and conformally coats the highly curved retina without compromising normal eye functions. The method allows 16-channel recordings from multiple types of RGCs with stable responses to visual stimuli for at least 2 weeks, and reveals circadian rhythms in RGC responses over multiple day/night cycles.

The Biomechanical Response of Normal and Glaucoma Human Sclera

2010 ◽  
Author(s):  
Baptiste Coudrillier ◽  
Kristin M. Myers ◽  
Thao D. Nguyen
Keyword(s):  
Retinal Ganglion Cells ◽  
Material Properties ◽  
Visual Information ◽  
Ganglion Cells ◽  
Retinal Ganglion ◽  
Progressive Degeneration ◽  
Biomechanical Response ◽  
Elevated Intraocular Pressure ◽  
The Relationship ◽  
The Brain

By 2010, 60 million people will have glaucoma, the second leading cause of blindness worldwide [1]. The disease is characterized by a progressive degeneration of the retinal ganglion cells (RGC), a type of neuron that transmits visual information to the brain. It is well know that elevated intraocular pressure (IOP) is a risk factor in the damage to the RGCs [3–5], but the relationship between the mechanical properties of the ocular connective tissue and how it affects cellular function is not well characterized. The cornea and the sclera are collage-rich structures that comprise the outer load-bearing shell of the eye. Their preferentially aligned collagen lamellae provide mechanical strength to resist ocular expansion. Previous uniaxial tension studies suggest that altered viscoelastic material properties of the eye wall play a role in glaucomatous damage [6].

Next-Generation Techniques for Analysis of Lamina Cribrosa Microstructure

2012 ◽  
Author(s):  
C. Ross Ethier ◽  
Richie Abel ◽  
E. A. Sander ◽  
John G. Flanagan ◽  
Michael Girard
Keyword(s):  
Risk Factor ◽  
Intraocular Pressure ◽  
Retinal Ganglion Cells ◽  
Visual Information ◽  
Ganglion Cells ◽  
Lamina Cribrosa ◽  
Retinal Ganglion ◽  
Irreversible Damage ◽  
Ocular Disorders ◽  
The Brain

Glaucoma describes a group of potentially blinding ocular disorders, afflicting c. 60 million people worldwide. Of these, c. 8 million are bilaterally blind, estimated to increase to 11 million by 2020. The central event in glaucoma is slow and irreversible damage of retinal ganglion cells, responsible for carrying visual information from the retina to the brain (Figure 1). Intraocular pressure (IOP) is a risk factor for glaucoma1–4, and significant, sustained IOP reduction is unequivocally beneficial in the clinical management of glaucoma patients2, 3, 5. Unfortunately, we do not understand how elevated IOP leads to the loss of retinal ganglion cells.

scholarly journals Molecular codes for cell type specification in Brn3 retinal ganglion cells

2017 ◽  
Vol 114 (20) ◽  
pp. E3974-E3983 ◽  
Author(s):  
Szilard Sajgo ◽  
Miruna Georgiana Ghinia ◽  
Matthew Brooks ◽  
Friedrich Kretschmer ◽  
Katherine Chuang ◽  
...  
Keyword(s):  
Retinal Ganglion Cells ◽  
Visual Information ◽  
Ganglion Cells ◽  
Neuronal Cell ◽  
Neuronal Morphology ◽  
Retinal Ganglion ◽  
Cell Type ◽  
Type Specification ◽  
The Brain ◽  
Combinatorial Code

Visual information is conveyed from the eye to the brain by distinct types of retinal ganglion cells (RGCs). It is largely unknown how RGCs acquire their defining morphological and physiological features and connect to upstream and downstream synaptic partners. The three Brn3/Pou4f transcription factors (TFs) participate in a combinatorial code for RGC type specification, but their exact molecular roles are still unclear. We use deep sequencing to define (i) transcriptomes of Brn3a- and/or Brn3b-positive RGCs, (ii) Brn3a- and/or Brn3b-dependent RGC transcripts, and (iii) transcriptomes of retinorecipient areas of the brain at developmental stages relevant for axon guidance, dendrite formation, and synaptogenesis. We reveal a combinatorial code of TFs, cell surface molecules, and determinants of neuronal morphology that is differentially expressed in specific RGC populations and selectively regulated by Brn3a and/or Brn3b. This comprehensive molecular code provides a basis for understanding neuronal cell type specification in RGCs.

scholarly journals Effects of Iron and Zinc on Mitochondria: Potential Mechanisms of Glaucomatous Injury

2021 ◽  
Vol 9 ◽  
Author(s):  
Jiahui Tang ◽  
Yehong Zhuo ◽  
Yiqing Li
Keyword(s):  
Ganglion Cell ◽  
Retinal Ganglion Cells ◽  
Visual Information ◽  
Ganglion Cells ◽  
Cell Damage ◽  
Current View ◽  
Retinal Ganglion ◽  
Mitochondrial Homeostasis ◽  
Iron And Zinc ◽  
The Brain

Glaucoma is the most substantial cause of irreversible blinding, which is accompanied by progressive retinal ganglion cell damage. Retinal ganglion cells are energy-intensive neurons that connect the brain and retina, and depend on mitochondrial homeostasis to transduce visual information through the brain. As cofactors that regulate many metabolic signals, iron and zinc have attracted increasing attention in studies on neurons and neurodegenerative diseases. Here, we summarize the research connecting iron, zinc, neuronal mitochondria, and glaucomatous injury, with the aim of updating and expanding the current view of how retinal ganglion cells degenerate in glaucoma, which can reveal novel potential targets for neuroprotection.

scholarly journals Atoh7-independent specification of retinal ganglion cell identity

2020 ◽  
Author(s):  
Justin Brodie-Kommit ◽  
Brian S. Clark ◽  
Qing Shi ◽  
Fion Shiau ◽  
Dong Won Kim ◽  
...  
Keyword(s):  
Visual Information ◽  
Ganglion Cells ◽  
Axonal Guidance ◽  
Retinal Ganglion ◽  
Rna Seq ◽  
Loss Of Function ◽  
Retinal Circuitry ◽  
The Brain ◽  
Deficient Mice ◽  
Modest Reduction

AbstractRetinal ganglion cells (RGCs), which relay visual information from the eye to the brain, are the first cell type generated during retinal neurogenesis. Loss of function of the transcription factor Atoh7, which is expressed in multipotent early neurogenic retinal progenitor cells, leads to a selective and near complete loss of RGCs. Atoh7 has thus been considered essential for conferring competence on progenitors to generate RGCs. However, when apoptosis is inhibited in Atoh7-deficient mice by loss of function of Bax, only a modest reduction in RGC number is observed. Single-cell RNA-Seq of Atoh7;Bax-deficient retinas shows that RGC differentiation is delayed, but that RGC precursors are grossly normal. Atoh7;Bax-deficient RGCs eventually mature, fire action potentials, and incorporate into retinal circuitry, but exhibit severe axonal guidance defects. This study reveals an essential role for Atoh7 in RGC survival, and demonstrates Atoh7-independent mechanisms for RGC specification.

scholarly journals Retinal Axon Interplay for Binocular Mapping

2021 ◽  
Vol 15 ◽  
Author(s):  
Coralie Fassier ◽  
Xavier Nicol
Keyword(s):  
Visual Information ◽  
Ganglion Cells ◽  
Mouse Retina ◽  
Retinal Ganglion ◽  
Genetic Approach ◽  
Developmental Mechanisms ◽  
Competitive Mechanisms ◽  
The Brain ◽  
Retinal Axon ◽  
Processing Of Visual Information

In most mammals, retinal ganglion cell axons from each retina project to both sides of the brain. The segregation of ipsi and contralateral projections into eye-specific territories in their main brain targets—the dorsolateral geniculate nucleus and the superior colliculus—is critical for the processing of visual information. The investigation of the developmental mechanisms contributing to the wiring of this binocular map in mammals identified competitive mechanisms between axons from each retina while interactions between axons from the same eye were challenging to explore. Studies in vertebrates lacking ipsilateral retinal projections demonstrated that competitive mechanisms also exist between axons from the same eye. The development of a genetic approach enabling the differential manipulation and labeling of neighboring retinal ganglion cells in a single mouse retina revealed that binocular map development does not only rely on axon competition but also involves a cooperative interplay between axons to stabilize their terminal branches. These recent insights into the developmental mechanisms shaping retinal axon connectivity in the brain will be discussed here.

scholarly journals Atoh7-independent specification of retinal ganglion cell identity

2021 ◽  
Vol 7 (11) ◽  
pp. eabe4983 ◽  
Author(s):  
Justin Brodie-Kommit ◽  
Brian S. Clark ◽  
Qing Shi ◽  
Fion Shiau ◽  
Dong Won Kim ◽  
...  
Keyword(s):  
Visual Information ◽  
Action Potentials ◽  
Ganglion Cells ◽  
Axonal Guidance ◽  
Retinal Ganglion ◽  
Loss Of Function ◽  
Cell Type ◽  
Retinal Circuitry ◽  
The Brain ◽  
Deficient Mice

Retinal ganglion cells (RGCs) relay visual information from the eye to the brain. RGCs are the first cell type generated during retinal neurogenesis. Loss of function of the transcription factorAtoh7, expressed in multipotent early neurogenic retinal progenitors leads to a selective and essentially complete loss of RGCs. Therefore,Atoh7is considered essential for conferring competence on progenitors to generate RGCs. Despite the importance of Atoh7 in RGC specification, we find that inhibiting apoptosis inAtoh7-deficient mice by loss of function ofBaxonly modestly reduces RGC numbers. Single-cell RNA sequencing ofAtoh7;Bax-deficient retinas shows that RGC differentiation is delayed but that the gene expression profile of RGC precursors is grossly normal.Atoh7;Bax-deficient RGCs eventually mature, fire action potentials, and incorporate into retinal circuitry but exhibit severe axonal guidance defects. This study reveals an essential role forAtoh7in RGC survival and demonstratesAtoh7-dependent andAtoh7-independent mechanisms for RGC specification.

scholarly journals Wiring the Binocular Visual Pathways

2019 ◽  
Vol 20 (13) ◽  
pp. 3282 ◽  
Author(s):  
Verónica Murcia-Belmonte ◽  
Lynda Erskine
Keyword(s):  
Visual Field ◽  
Retinal Ganglion Cells ◽  
Visual Information ◽  
Ganglion Cells ◽  
Optic Chiasm ◽  
Contralateral Side ◽  
Topographic Maps ◽  
Retinal Ganglion ◽  
Brain Hemispheres ◽  
The Brain

Retinal ganglion cells (RGCs) extend axons out of the retina to transmit visual information to the brain. These connections are established during development through the navigation of RGC axons along a relatively long, stereotypical pathway. RGC axons exit the eye at the optic disc and extend along the optic nerves to the ventral midline of the brain, where the two nerves meet to form the optic chiasm. In animals with binocular vision, the axons face a choice at the optic chiasm—to cross the midline and project to targets on the contralateral side of the brain, or avoid crossing the midline and project to ipsilateral brain targets. Ipsilaterally and contralaterally projecting RGCs originate in disparate regions of the retina that relate to the extent of binocular overlap in the visual field. In humans virtually all RGC axons originating in temporal retina project ipsilaterally, whereas in mice, ipsilaterally projecting RGCs are confined to the peripheral ventrotemporal retina. This review will discuss recent advances in our understanding of the mechanisms regulating specification of ipsilateral versus contralateral RGCs, and the differential guidance of their axons at the optic chiasm. Recent insights into the establishment of congruent topographic maps in both brain hemispheres also will be discussed.

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