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Cells
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Molecular Biology of Retinal Ganglion Cells
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Molecular Biology of Retinal Ganglion Cells

A special issue of Cells (ISSN 2073-4409).

Deadline for manuscript submissions: closed (15 August 2020) | Viewed by 37294

Special Issue Editor

Prof. Dr. Béla Völgyi

E-Mail Website
Guest Editor
Retinal Neurobiology Research Group, University of Pecs, Pecs, Hungary
Interests: vision; retinal signal processing; ganglion cells; population coding; electrical synapses; parallel signaling; morphological/functional classification
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleague,

Retinal ganglion cells (RGCs) are the output neurons of the vertebrate retina and in addition to integrating information and passing it to target neurons in retinorecipient brain centers, they also perform a serious computation by which they encode signals into trains of action potentials. This mechanism requires the coordinated expression, activation, modulation, deactivation, and disintegration of molecules that partake in RGC signaling, homeostatic processes, maintenance of cellular integrity, and adaptation of cells to the changing conditions. While many of these molecular constituents are generally expressed by most neurons in the central nervous system, expression of others is characteristic of RGCs, and together they form the RGC molecular fingerprint. As RGCs form over 20 morphological/functional subtypes, it is expected that their fingerprints display subtype specificity that can be utilized for identification. Cellular fingerprints, however, are not ‘static’ but can change during development, at times of pathological insults or even through normal functioning. This Special Issue, published on an Open Access platform, aims to bring together a collection of original research papers and review articles addressing the ever-growing field of the molecular biology of retinal ganglion cells. Our goal is to encourage scientists in the corresponding field to contribute to this Special Issue with their related work. Suggested potential topics include (but are not limited to): Subtype specific RGC marker molecules, molecules of RGC signaling, and disease-induced molecular changes.

Prof. Béla Völgyi
Guest Editor

Manuscript Submission Information

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Keywords

  • ganglion cells
  • molecular phenotyping
  • intracellular cascade
  • signal processing
  • development
  • pathology
  • adaptation
  • circadian rhythm

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Published Papers (9 papers)

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Editorial

Jump to: Research, Review

3 pages, 201 KiB  
Editorial
Molecular Biology of Retinal Ganglion Cells
by Béla Völgyi
Cells 2020, 9(11), 2483; https://doi.org/10.3390/cells9112483 - 15 Nov 2020
Cited by 12 | Viewed by 1857
Abstract
The main goal of this thematic issue was to bring both original research papers and reviews together to provide an insight into the rather broad topic of molecular biology of retinal ganglion cells (RGCs) [...] Full article
(This article belongs to the Special Issue Molecular Biology of Retinal Ganglion Cells)

Research

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19 pages, 7097 KiB  
Article
Intravitreal Co-Administration of GDNF and CNTF Confers Synergistic and Long-Lasting Protection against Injury-Induced Cell Death of Retinal Ganglion Cells in Mice
by Simon Dulz, Mahmoud Bassal, Kai Flachsbarth, Kristoffer Riecken, Boris Fehse, Stefanie Schlichting, Susanne Bartsch and Udo Bartsch
Cells 2020, 9(9), 2082; https://doi.org/10.3390/cells9092082 - 11 Sep 2020
Cited by 25 | Viewed by 3295
Abstract
We have recently demonstrated that neural stem cell-based intravitreal co-administration of glial cell line-derived neurotrophic factor (GDNF) and ciliary neurotrophic factor (CNTF) confers profound protection to injured retinal ganglion cells (RGCs) in a mouse optic nerve crush model, resulting in the survival of [...] Read more.
We have recently demonstrated that neural stem cell-based intravitreal co-administration of glial cell line-derived neurotrophic factor (GDNF) and ciliary neurotrophic factor (CNTF) confers profound protection to injured retinal ganglion cells (RGCs) in a mouse optic nerve crush model, resulting in the survival of ~38% RGCs two months after the nerve lesion. Here, we analyzed whether this neuroprotective effect is long-lasting and studied the impact of the pronounced RGC rescue on axonal regeneration. To this aim, we co-injected a GDNF- and a CNTF-overexpressing neural stem cell line into the vitreous cavity of adult mice one day after an optic nerve crush and determined the number of surviving RGCs 4, 6 and 8 months after the lesion. Remarkably, we found no significant decrease in the number of surviving RGCs between the successive analysis time points, indicating that the combined administration of GDNF and CNTF conferred lifelong protection to injured RGCs. While the simultaneous administration of GDNF and CNTF stimulated pronounced intraretinal axon growth when compared to retinas treated with either factor alone, numbers of regenerating axons in the distal optic nerve stumps were similar in animals co-treated with both factors and animals treated with CNTF only. Full article
(This article belongs to the Special Issue Molecular Biology of Retinal Ganglion Cells)
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20 pages, 8434 KiB  
Article
Spatial Expression Pattern of the Major Ca2+-Buffer Proteins in Mouse Retinal Ganglion Cells
by Tamás Kovács-Öller, Gergely Szarka, Ádám J. Tengölics, Alma Ganczer, Boglárka Balogh, Edina Szabó-Meleg, Miklós Nyitrai and Béla Völgyi
Cells 2020, 9(4), 792; https://doi.org/10.3390/cells9040792 - 25 Mar 2020
Cited by 9 | Viewed by 3590
Abstract
The most prevalent Ca2+-buffer proteins (CaBPs: parvalbumin—PV; calbindin—CaB; calretinin—CaR) are widely expressed by various neurons throughout the brain, including the retinal ganglion cells (RGCs). Even though their retinal expression has been extensively studied, a coherent assessment of topographical variations is missing. [...] Read more.
The most prevalent Ca2+-buffer proteins (CaBPs: parvalbumin—PV; calbindin—CaB; calretinin—CaR) are widely expressed by various neurons throughout the brain, including the retinal ganglion cells (RGCs). Even though their retinal expression has been extensively studied, a coherent assessment of topographical variations is missing. To examine this, we performed immunohistochemistry (IHC) in mouse retinas. We found variability in the expression levels and cell numbers for CaR, with stronger and more numerous labels in the dorso-central area. CaBP+ cells contributed to RGCs with all soma sizes, indicating heterogeneity. We separated four to nine RGC clusters in each area based on expression levels and soma sizes. Besides the overall high variety in cluster number and size, the peripheral half of the temporal retina showed the greatest cluster number, indicating a better separation of RGC subtypes there. Multiple labels showed that 39% of the RGCs showed positivity for a single CaBP, 30% expressed two CaBPs, 25% showed no CaBP expression, and 6% expressed all three proteins. Finally, we observed an inverse relation between CaB and CaR expression levels in CaB/CaR dual- and CaB/CaR/PV triple-labeled RGCs, suggesting a mutual complementary function. Full article
(This article belongs to the Special Issue Molecular Biology of Retinal Ganglion Cells)
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22 pages, 4066 KiB  
Article
The Susceptibility of Retinal Ganglion Cells to Optic Nerve Injury is Type Specific
by Ning Yang, Brent K Young, Ping Wang and Ning Tian
Cells 2020, 9(3), 677; https://doi.org/10.3390/cells9030677 - 10 Mar 2020
Cited by 32 | Viewed by 4958
Abstract
Retinal ganglion cell (RGC) death occurs in many eye diseases, such as glaucoma and traumatic optic neuropathy (TON). Increasing evidence suggests that the susceptibility of RGCs varies to different diseases in an RGC type-dependent manner. We previously showed that the susceptibility of several [...] Read more.
Retinal ganglion cell (RGC) death occurs in many eye diseases, such as glaucoma and traumatic optic neuropathy (TON). Increasing evidence suggests that the susceptibility of RGCs varies to different diseases in an RGC type-dependent manner. We previously showed that the susceptibility of several genetically identified RGC types to N-methyl-D-aspartate (NMDA) excitotoxicity differs significantly. In this study, we characterize the susceptibility of the same RGC types to optic nerve crush (ONC). We show that the susceptibility of these RGC types to ONC varies significantly, in which BD-RGCs are the most resistant RGC type while W3-RGCs are the most sensitive cells to ONC. We also show that the survival rates of BD-RGCs and J-RGCs after ONC are significantly higher than their survival rates after NMDA excitotoxicity. These results are consistent with the conclusion that the susceptibility of RGCs to ONC varies in an RGC type-dependent manner. Further, the susceptibilities of the same types of RGCs to ONC and NMDA excitotoxicity are significantly different. These are valuable insights for understanding of the selective susceptibility of RGCs to various pathological insults and the development of a strategy to protect RGCs from death in disease conditions. Full article
(This article belongs to the Special Issue Molecular Biology of Retinal Ganglion Cells)
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19 pages, 3427 KiB  
Article
Defocused Images Change Multineuronal Firing Patterns in the Mouse Retina
by Seema Banerjee, Qin Wang, Chung Him So and Feng Pan
Cells 2020, 9(3), 530; https://doi.org/10.3390/cells9030530 - 25 Feb 2020
Cited by 10 | Viewed by 3512
Abstract
Myopia is a major public health problem, affecting one third of the population over 12 years old in the United States and more than 80% of people in Hong Kong. Myopia is attributable to elongation of the eyeball in response to defocused images [...] Read more.
Myopia is a major public health problem, affecting one third of the population over 12 years old in the United States and more than 80% of people in Hong Kong. Myopia is attributable to elongation of the eyeball in response to defocused images that alter eye growth and refraction. It is known that the retina can sense the focus of an image, but the effects of defocused images on signaling of population of retinal ganglion cells (RGCs) that account either for emmetropization or refractive errors has still to be elucidated. Thorough knowledge of the underlying mechanisms could provide insight to understanding myopia. In this study, we found that focused and defocused images can change both excitatory and inhibitory conductance of ON alpha, OFF alpha and ON–OFF retinal ganglion cells in the mouse retina. The firing patterns of population of RGCs vary under the different powers of defocused images and can be affected by dopamine receptor agonists/antagonists’ application. OFF-delayed RGCs or displaced amacrine cells (dACs) with time latency of more than 0.3 s had synchrony firing with other RGCs and/or dACs. These spatial synchrony firing patterns between OFF-delayed cell and other RGCs/dACs were significantly changed by defocused image, which may relate to edge detection. The results suggested that defocused images induced changes in the multineuronal firing patterns and whole cell conductance in the mouse retina. The multineuronal firing patterns can be affected by dopamine receptors’ agonists and antagonists. Synchronous firing of OFF-delayed cells is possibly related to edge detection, and understanding of this process may reveal a potential therapeutic target for myopia patients. Full article
(This article belongs to the Special Issue Molecular Biology of Retinal Ganglion Cells)
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14 pages, 2431 KiB  
Article
Norrin Protects Retinal Ganglion Cells from Excitotoxic Damage via the Induction of Leukemia Inhibitory Factor
by Stefan Kassumeh, Stephanie Leopold, Rudolf Fuchshofer, Carina N. Thomas, Siegfried G. Priglinger, Ernst R. Tamm and Andreas Ohlmann
Cells 2020, 9(2), 277; https://doi.org/10.3390/cells9020277 - 23 Jan 2020
Cited by 7 | Viewed by 3309
Abstract
Purpose: To investigate whether and how leukemia inhibitory factor (Lif) is involved in mediating the neuroprotective effects of Norrin on retinal ganglion cells (RGC) following excitotoxic damage. Norrin is a secreted protein that protects RGC from N-methyl-d-aspartate (NMDA)-mediated excitotoxic damage, [...] Read more.
Purpose: To investigate whether and how leukemia inhibitory factor (Lif) is involved in mediating the neuroprotective effects of Norrin on retinal ganglion cells (RGC) following excitotoxic damage. Norrin is a secreted protein that protects RGC from N-methyl-d-aspartate (NMDA)-mediated excitotoxic damage, which is accompanied by increased expression of protective factors such as Lif, Edn2 and Fgf2. Methods: Lif-deficient mice were injected with NMDA in one eye and NMDA plus Norrin into the other eye. RGC damage was investigated and quantified by TUNEL labeling 24 h after injection. Retinal mRNA expression was analyzed by quantitative real-time polymerase chain reaction following retinal treatment. Results: After intravitreal injection of NMDA and Norrin in wild-type mice approximately 50% less TUNEL positive cells were observed in the RGC layer when compared to NMDA-treated littermates, an effect which was lost in Lif-deficient mice. The mRNA expression for Gfap, a marker for Müller cell gliosis, as well as Edn2 and Fgf2 was induced in wild-type mice following NMDA/Norrin treatment but substantially blocked in Lif-deficient mice. Conclusions: Norrin mediates its protective properties on RGC via Lif, which is required to enhance Müller cell gliosis and to induce protective factors such as Edn2 or Fgf2. Full article
(This article belongs to the Special Issue Molecular Biology of Retinal Ganglion Cells)
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21 pages, 2809 KiB  
Article
Defocused Image Changes Signaling of Ganglion Cells in the Mouse Retina
by Feng Pan
Cells 2019, 8(7), 640; https://doi.org/10.3390/cells8070640 - 26 Jun 2019
Cited by 20 | Viewed by 5307
Abstract
Myopia is a substantial public health problem worldwide. Although it is known that defocused images alter eye growth and refraction, their effects on retinal ganglion cell (RGC) signaling that lead to either emmetropization or refractive errors have remained elusive. This study aimed to [...] Read more.
Myopia is a substantial public health problem worldwide. Although it is known that defocused images alter eye growth and refraction, their effects on retinal ganglion cell (RGC) signaling that lead to either emmetropization or refractive errors have remained elusive. This study aimed to determine if defocused images had an effect on signaling of RGCs in the mouse retina. ON and OFF alpha RGCs and ON–OFF RGCs were recorded from adult C57BL/6J wild-type mice. A mono green organic light-emitting display presented images generated by PsychoPy. The defocused images were projected on the retina under a microscope. Dark-adapted mouse RGCs were recorded under different powers of projected defocused images on the retina. Compared with focused images, defocused images showed a significantly decreased probability of spikes. More than half of OFF transient RGCs and ON sustained RGCs showed disparity in responses to the magnitude of plus and minus optical defocus (although remained RGCs we tested exhibited similar response to both types of defocus). ON and OFF units of ON–OFF RGCs also responded differently in the probability of spikes to defocused images and spatial frequency images. After application of a gap junction blocker, the probability of spikes of RGCs decreased with the presence of optical defocused image. At the same time, the RGCs also showed increased background noise. Therefore, defocused images changed the signaling of some ON and OFF alpha RGCs and ON–OFF RGCs in the mouse retina. The process may be the first step in the induction of myopia development. It appears that gap junctions also play a key role in this process. Full article
(This article belongs to the Special Issue Molecular Biology of Retinal Ganglion Cells)
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Review

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14 pages, 1125 KiB  
Review
Glaucoma: A Degenerative Optic Neuropathy Related to Neuroinflammation?
by Stéphane Mélik Parsadaniantz, Annabelle Réaux-le Goazigo, Anaïs Sapienza, Christophe Habas and Christophe Baudouin
Cells 2020, 9(3), 535; https://doi.org/10.3390/cells9030535 - 25 Feb 2020
Cited by 58 | Viewed by 7385
Abstract
Glaucoma is one of the leading causes of irreversible blindness in the world and remains a major public health problem. To date, incomplete knowledge of this disease’s pathophysiology has resulted in current therapies (pharmaceutical or surgical) unfortunately having only a slowing effect on [...] Read more.
Glaucoma is one of the leading causes of irreversible blindness in the world and remains a major public health problem. To date, incomplete knowledge of this disease’s pathophysiology has resulted in current therapies (pharmaceutical or surgical) unfortunately having only a slowing effect on disease progression. Recent research suggests that glaucomatous optic neuropathy is a disease that shares common neuroinflammatory mechanisms with “classical” neurodegenerative pathologies. In addition to the death of retinal ganglion cells (RGCs), neuroinflammation appears to be a key element in the progression and spread of this disease. Indeed, early reactivity of glial cells has been observed in the retina, but also in the central visual pathways of glaucoma patients and in preclinical models of ocular hypertension. Moreover, neuronal lesions are not limited to retinal structure, but also occur in central visual pathways. This review summarizes and puts into perspective the experimental and clinical data obtained to date to highlight the need to develop neuroprotective and immunomodulatory therapies to prevent blindness in glaucoma patients. Full article
(This article belongs to the Special Issue Molecular Biology of Retinal Ganglion Cells)
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Graphical abstract

11 pages, 732 KiB  
Review
Species Differences in the Nutrition of Retinal Ganglion Cells among Mammals Frequently Used as Animal Models
by Christian Albrecht May
Cells 2019, 8(10), 1254; https://doi.org/10.3390/cells8101254 - 14 Oct 2019
Cited by 3 | Viewed by 3131
Abstract
The diffusion rate for proper nutrition of the inner retina depends mainly on four factors which are discussed in this review: 1. The diffusion distance between blood and retinal ganglion cells shows morphological variants in different mammalian species, namely a choroidal nutrition type, [...] Read more.
The diffusion rate for proper nutrition of the inner retina depends mainly on four factors which are discussed in this review: 1. The diffusion distance between blood and retinal ganglion cells shows morphological variants in different mammalian species, namely a choroidal nutrition type, a retinal nutrition type, and a mixture of both types. 2. Low oxygen concentration levels in the inner retina force the diffusion of oxygen especially in the choroidal nutrition type. Other nutrients might be supplied by surrounding cells, mainly Müller cells. 3. Diffusion in the eye is influenced by the intraocular pressure, which is vital for the retinal ganglion cells but might also influence their proper function. Again, the nutrition types established might explain the differences in normal intraocular pressure levels among different species. 4. Temperature is a critical feature in the eye which has to be buffered to avoid neuronal damage. The most effective buffer system is the increased blood turnover in the choroid which has to be established in all species. Full article
(This article belongs to the Special Issue Molecular Biology of Retinal Ganglion Cells)
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