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Cells
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Stem Cells in Retinal or Optic Nerve Disease and Development
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Stem Cells in Retinal or Optic Nerve Disease and Development

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Stem Cells".

Deadline for manuscript submissions: closed (30 September 2020) | Viewed by 8341

Special Issue Editors

Prof. Dr. Stefan Liebau

E-Mail Website
Guest Editor
Institute of Neuroanatomy & Developmental Biology INDB, Eberhard Karls University Tübingen, Österbergstr. 3, 72074 Tubingen, Germany
Interests: pluripotent stem cells; neurosensory systems; stem cell differentiation; neuroplasticity; neurogenesis; retinal organoids; gene therapy; organ-on-chip
Special Issues, Collections and Topics in MDPI journals
Prof. Peter Loskill

E-Mail Website
Guest Editor
The µOrgano-Lab, University of Tübingen, Tübingen, Germany
Interests: organ-on-chip; tissue engineering; microfabrication; pharmaceutical R&D; 3R
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Stem cell research in the field of ophthalmology provides novel paths to understand and provide future therapeutic approaches in ophthalmology. Human pluripotent stem cell-derived 3-dimensional organ-like structures (organoids) have been shown to reflect distinct tissues, such as subsystems of the central nervous system, including the retina. Retinal organoids, also called “eyes in the dish”, resemble rudimentary eyecup-like structures with a retinal layering close to the physiological conditions. Retinal organoids contain all relevant retinal cells, such as ganglion cells, amacrine cells, horizontal cells bipolar cells, Mueller glia, as well as rods and cones. This system represents a unique tool to investigate human as well as individual retinal development and function, respectively. Concerning the optical nerve and further connections to the respective brain areas, only a few therapeutic ideas have been developed, and regeneration of the optical nerve is still of high importance in the clinical field. Basic research using stem cells may be implemented into basic and clinical research. We aim for submissions for the Special Issue including studies using stem cells of any kind in the field of developmental and clinical research.

Prof. Stefan Liebau
Prof. Peter Loskill
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • stem cell
  • organoids
  • retina
  • human pluripotent stem cell
  • retinal development
  • optic nerve
  • regina models

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Published Papers (2 papers)

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Research

14 pages, 9177 KiB  
Article
Establishment of a Rapid Lesion-Controllable Retinal Degeneration Monkey Model for Preclinical Stem Cell Therapy
by Guanjie Gao, Liwen He, Shengxu Liu, Dandan Zheng, Xiaojing Song, Wenxin Zhang, Minzhong Yu, Guangwei Luo and Xiufeng Zhong
Cells 2020, 9(11), 2468; https://doi.org/10.3390/cells9112468 - 13 Nov 2020
Cited by 5 | Viewed by 2841
Abstract
Background: Retinal degenerative disorders (RDs) are the main cause of blindness without curable treatment. Our previous studies have demonstrated that human-induced pluripotent stem cells can differentiate into retinal organoids with all subtypes of retina, which provides huge promise for treating these diseases. Before [...] Read more.
Background: Retinal degenerative disorders (RDs) are the main cause of blindness without curable treatment. Our previous studies have demonstrated that human-induced pluripotent stem cells can differentiate into retinal organoids with all subtypes of retina, which provides huge promise for treating these diseases. Before these methods can be realized, RD animal models are required to evaluate the safety and efficacy of stem cell therapy and to develop the surgical tools and procedures for cell transplantation in patients. This study involved the development of a monkey model of RD with controllable lesion sites, which can be rapidly prepared for the study of preclinical stem cell therapy among other applications. Methods: Sodium nitroprusside (SNP) in three doses was delivered into the monkey eye by subretinal injection (SI), and normal saline was applied as control. Structural and functional changes of the retinas were evaluated via multimodal imaging techniques and multifocal electroretinography (mfERG) before and after the treatment. Histological examination was performed to identify the target layer of the affected retina. The health status of monkeys was monitored during the experiment. Results: Well-defined lesions with various degrees of retinal degeneration were induced at the posterior pole of retina as early as 7 days after SNP SI. The damage of SNP was dose dependent. In general, 0.05 mM SNP caused mild structural changes in the retina; 0.1 mM SNP led to the loss of outer retinal layers, including the outer plexiform layer (OPL), outer nuclear layer (ONL), and retinal pigment epithelium (RPE); while 0.2 mM SNP impacted the entire layer of the retina and choroid. MfERG showed reduced amplitude in the damaged region. The structural and functional damages were not recovered at 7-month follow-up. Conclusion: A rapidly induced lesion site-controllable retinal degeneration monkey model was established by the subretinal administration of SNP, of which the optimal dose is 0.1 mM. This monkey model mimics the histological changes of advanced RDs and provides a valuable platform for preclinical assessment of stem cell therapy for RDs. Full article
(This article belongs to the Special Issue Stem Cells in Retinal or Optic Nerve Disease and Development)
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17 pages, 4831 KiB  
Article
Effects of Adult Müller Cells and Their Conditioned Media on the Survival of Stem Cell-Derived Retinal Ganglion Cells
by Xandra Pereiro, Adam M. Miltner, Anna La Torre and Elena Vecino
Cells 2020, 9(8), 1759; https://doi.org/10.3390/cells9081759 - 22 Jul 2020
Cited by 12 | Viewed by 4733
Abstract
Retinal neurons, particularly retinal ganglion cells (RGCs), are susceptible to the degenerative damage caused by different inherited conditions and environmental insults, leading to irreversible vision loss and, ultimately, blindness. Numerous strategies are being tested in different models of degeneration to restore vision and, [...] Read more.
Retinal neurons, particularly retinal ganglion cells (RGCs), are susceptible to the degenerative damage caused by different inherited conditions and environmental insults, leading to irreversible vision loss and, ultimately, blindness. Numerous strategies are being tested in different models of degeneration to restore vision and, in recent years, stem cell technologies have offered novel avenues to obtain donor cells for replacement therapies. To date, stem cell–based transplantation in the retina has been attempted as treatment for photoreceptor degeneration, but the same tools could potentially be applied to other retinal cell types, including RGCs. However, RGC-like cells are not an abundant cell type in stem cell–derived cultures and, often, these cells degenerate over time in vitro. To overcome this limitation, we have taken advantage of the neuroprotective properties of Müller glia (one of the main glial cell types in the retina) and we have examined whether Müller glia and the factors they secrete could promote RGC-like cell survival in organoid cultures. Accordingly, stem cell-derived RGC-like cells were co-cultured with adult Müller cells or Müller cell-conditioned media was added to the cultures. Remarkably, RGC-like cell survival was substantially enhanced in both culture conditions, and we also observed a significant increase in their neurite length. Interestingly, Atoh7, a transcription factor required for RGC development, was up-regulated in stem cell-derived organoids exposed to conditioned media, suggesting that Müller cells may also enhance the survival of retinal progenitors and/or postmitotic precursor cells. In conclusion, Müller cells and the factors they release promote organoid-derived RGC-like cell survival, neuritogenesis, and possibly neuronal maturation. Full article
(This article belongs to the Special Issue Stem Cells in Retinal or Optic Nerve Disease and Development)
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