scholarly journals Atoh7-independent specification of retinal ganglion cell identity

Author(s):  
Justin Brodie-Kommit ◽  
Brian S. Clark ◽  
Qing Shi ◽  
Fion Shiau ◽  
Dong Won Kim ◽  
...  

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.

2021 ◽  
Vol 7 (11) ◽  
pp. eabe4983 ◽  
Author(s):  
Justin Brodie-Kommit ◽  
Brian S. Clark ◽  
Qing Shi ◽  
Fion Shiau ◽  
Dong Won Kim ◽  
...  

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.


Science ◽  
2018 ◽  
Vol 360 (6396) ◽  
pp. 1447-1451 ◽  
Author(s):  
Guosong Hong ◽  
Tian-Ming Fu ◽  
Mu Qiao ◽  
Robert D. Viveros ◽  
Xiao Yang ◽  
...  

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.


Author(s):  
Baptiste Coudrillier ◽  
Kristin M. Myers ◽  
Thao D. Nguyen

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].


Author(s):  
C. Ross Ethier ◽  
Richie Abel ◽  
E. A. Sander ◽  
John G. Flanagan ◽  
Michael Girard

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.


2017 ◽  
Vol 114 (20) ◽  
pp. E3974-E3983 ◽  
Author(s):  
Szilard Sajgo ◽  
Miruna Georgiana Ghinia ◽  
Matthew Brooks ◽  
Friedrich Kretschmer ◽  
Katherine Chuang ◽  
...  

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.


Author(s):  
Jiahui Tang ◽  
Yehong Zhuo ◽  
Yiqing Li

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.


2006 ◽  
Vol 95 (2) ◽  
pp. 837-849 ◽  
Author(s):  
Hao Sun ◽  
Hannah E. Smithson ◽  
Qasim Zaidi ◽  
Barry B. Lee

The specificity of cone inputs to ganglion cells has implications for the development of retinal connections and the nature of information transmitted to higher areas of the brain. We introduce a rapid and precise method for measuring signs and magnitudes of cone inputs to visual neurons. Colors of stimuli are modulated around circumferences of three color planes in clockwise and counterclockwise directions. For each neuron, the projection of the preferred vector in each plane was estimated by averaging the response phases to clockwise and counterclockwise modulation. The signs and weights of cone inputs were derived directly from the preferred vectors. The efficiency of the method enables us to measure cone inputs at different temporal frequencies and short-wavelength-sensitive (S) cone adaptation levels. The results show that S-cone inputs to the parvocellular and magnocellular ganglion cells are negligible, which implies underlying connectional specificity in the retinal circuitry.


2020 ◽  
Author(s):  
Corinne Beier ◽  
Ze Zhang ◽  
Maria Yurgel ◽  
Samer Hattar

ABSTRACTRetinal ganglion cells (RGCs), the output neurons of the retina, allow us to perceive our visual environment. RGCs respond to rod/cone input through the retinal circuitry, however, a small population of RGCs are in addition intrinsically photosensitive (ipRGCs) and project to unique targets in the brain to modulate a broad range of subconscious visual behaviors such as pupil constriction and circadian photoentrainment. Despite the discovery of ipRGCs nearly two decades ago, there is still little information about how or if conventional RGCs (non-ipRGCs) target ipRGC-recipient nuclei to influence subconscious visual behavior. Using a dual recombinase color strategy, we showed that conventional RGCs innervate many subconscious ipRGC-recipient nuclei, apart from the suprachiasmatic nucleus. We revealed previously unrecognized stratification patterns of retinal innervation from ipRGCs and conventional RGCs in the ventral portion of the lateral geniculate nucleus. Further, we found that the percent innervation of ipRGCs and conventional RGCs across ipsi- and contralateral nuclei differ. Our data provide a blueprint to understand how conventional RGCs and ipRGCs innervate different brain regions to influence subconscious visual behaviors.


2021 ◽  
Vol 15 ◽  
Author(s):  
Coralie Fassier ◽  
Xavier Nicol

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.


2019 ◽  
Vol 20 (13) ◽  
pp. 3282 ◽  
Author(s):  
Verónica Murcia-Belmonte ◽  
Lynda Erskine

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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