Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

Journal Browser

Retina Degeneration, Neuroprotection and Repair

Special Issue Editors
Special Issue Information
Keywords
Published Papers

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (30 November 2021) | Viewed by 40024

Share This Special Issue

Special Issue Editors

Dr. Arturo Ortín-Martínez

E-Mail Website
Guest Editor

Donald K. Johnson Eye Institute, Krembil Research Institute, University Health Network, Toronto, ON, Canada
Interests: retina; photoreceptors; retinal ganglion cells; degeneration; neuroprotection; regenerative medicine; cell therapy; macular degeneration; retinitis pigmentosa; glaucoma

Dr. Luis Alarcon-Martinez

E-Mail Website
Guest Editor

Department of Neuroscience, Université de Montréal, Montréal, QC H3C 3J7, Canada
Interests: retina; vascular system; neurovascular coupling; pericytes; functional hyperaemia; electroretinography; two-photon microscopy

Dr. Sandra Petrus-Reurer

E-Mail
Guest Editor

University of Cambridge, Cambridge, UK
Interests: retina; retinal pigment epithelial cells; human embryonic stem cells; RPE differentiation; cellular repair; retinal progenitor; preclinical animal model; macular degeneration; immunology of allorejection; immunomodulation

Special Issue Information

Dear Colleagues,

We are pleased to announce the upcoming Special Issue “Retina Neurodegeneration, Neuroprotection and Repair”.

Globally, 1.2 billion people live with blindness or a vision impairment that could not be prevented or addressed. Age-related macular degeneration (170 million), glaucoma (7 million), diabetic retinopathy (3 million), and retinitis pigmentosa (1.5 million) are some of the main pathologies leading to irreversible visual impairment and blindness.

The capacity for endogenous repair is effectively absent in the mammalian central nervous system, including the retina, which exhibits no intrinsic regenerative capacities; therefore, retinal degenerative diseases such as those listed above result in permanent and irreversible impairment.

Currently, great scientific efforts are focused on bringing sight and a better understanding of: i) the mechanisms that lead to the degeneration of key retinal cell populations such as photoreceptors and retinal ganglion cells; ii) the neuroinflammatory response that accompanied the degeneration, involving retinal microglia cells and inflammatory mediators; iii) circulatory blood flow implications in the progression of the neurodegenerative process; iv) identification of new molecular targets to delay or impede the progression of the degeneration; v) regenerative medicine approaches such as gene therapy and cell replacement strategies to restore function loss.

This Special Issue shall cover results of studies using experimental models (animal or cell culture models) to investigate the mechanism of progression of retina degeneration and cell death, strategies to stop or delay the progression, including neuroprotective pharmaceutical target and/or therapeutic approaches based on regenerative medicine such as gene and cell therapy, to restore vision.

We warmly welcome short communications, original research articles, and review articles for this Special Issue.

Dr. Arturo Ortín-Martínez
Dr. Luis Alarcón-Martínez
Dr. Sandra Petrus-Reurer
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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

retina
age-related macular degeneration
retinitis pigmentosa
glaucoma
photoreceptors
retinal ganglion cells
degeneration
neuroprotection
neuroinflammation
retina blood flow
regenerative medicine
gene therapy
transplantation
cell therapy

Published Papers (13 papers)

Download All Papers

Research

Jump to: Review

20 pages, 5297 KiB

Open AccessArticle

Glial Cell Activation and Oxidative Stress in Retinal Degeneration Induced by β-Alanine Caused Taurine Depletion and Light Exposure

by Ana Martínez-Vacas, Johnny Di Pierdomenico, Francisco J. Valiente-Soriano, Manuel Vidal-Sanz, Serge Picaud, María Paz Villegas-Pérez and Diego García-Ayuso

Int. J. Mol. Sci. 2022, 23(1), 346; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23010346 - 29 Dec 2021

Cited by 10 | Viewed by 2326

Abstract

We investigate glial cell activation and oxidative stress induced by taurine deficiency secondary to β-alanine administration and light exposure. Two months old Sprague-Dawley rats were divided into a control group and three experimental groups that were treated with 3% β-alanine in drinking water (taurine depleted) for two months, light exposed or both. Retinal and external thickness were measured in vivo at baseline and pre-processing with Spectral-Domain Optical Coherence Tomography (SD-OCT). Retinal cryostat cross sections were immunodetected with antibodies against various antigens to investigate microglial and macroglial cell reaction, photoreceptor outer segments, synaptic connections and oxidative stress. Taurine depletion caused a decrease in retinal thickness, shortening of photoreceptor outer segments, microglial cell activation, oxidative stress in the outer and inner nuclear layers and the ganglion cell layer and synaptic loss. These events were also observed in light exposed animals, which in addition showed photoreceptor death and macroglial cell reactivity. Light exposure under taurine depletion further increased glial cell reaction and oxidative stress. Finally, the retinal pigment epithelial cells were Fluorogold labeled and whole mounted, and we document that taurine depletion impairs their phagocytic capacity. We conclude that taurine depletion causes cell damage to various retinal layers including retinal pigment epithelial cells, photoreceptors and retinal ganglion cells, and increases the susceptibility of the photoreceptor outer segments to light damage. Thus, beta-alanine supplements should be used with caution. Full article

(This article belongs to the Special Issue Retina Degeneration, Neuroprotection and Repair)

► Show Figures

Figure 1

19 pages, 12348 KiB

Open AccessArticle

Ly6c as a New Marker of Mouse Blood Vessels: Qualitative and Quantitative Analyses on Intact and Ischemic Retinas

by Marina Martínez-Carmona, Fernando Lucas-Ruiz, Alejandro Gallego-Ortega, Caridad Galindo-Romero, María Norte-Muñoz, María José González-Riquelme, Francisco J. Valiente-Soriano, Manuel Vidal-Sanz and Marta Agudo-Barriuso

Int. J. Mol. Sci. 2022, 23(1), 19; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23010019 - 21 Dec 2021

Cited by 3 | Viewed by 2718

Abstract

Ly6c is an antigen commonly used to differentiate between classical and non-classical monocytes/macrophages. Here we show its potential as a marker of the mouse vasculature, particularly of the retinal vascular plexuses. Ly6c was immunodetected in several tissues of C57BL/6 mice using isolectin IB4 as the control of vasculature staining. In the retina, Ly6c expression was analyzed qualitatively and quantitatively in intact, ischemic, and contralateral retinas from 0 to 30 days after the insult. Ly6c expression was observed in all organs and tissues tested, with a brighter signal and more homogeneous staining than the IB4. In the retinas, Ly6c was well expressed, allowing a detailed study of their anatomy. The three retinal plexuses were morphologically different, and from the superficial to the deep one occupied 15 ± 2, 24 ± 7, and 38 ± 1.4 percent of the retinal surface, respectively. In the injured retinas, there was extravasation of the classically activated monocyte/macrophages (Ly6c^high) and the formation of new vessels in the superficial plexus, increasing the area occupied by it to 25 ± 1%. In the contralateral retinas, the superficial plexus area decreased gradually, reaching significance at 30 days, and Ly6c expression progressively disappeared in the intermediate and deep plexuses. Although the role of Ly6c in vascular endothelial cell function is still not completely understood, we demonstrate here that Ly6c can be used as a new specific marker of the mouse vasculature and to assess, qualitatively and quantitatively, vascular changes in health and disease. Full article

(This article belongs to the Special Issue Retina Degeneration, Neuroprotection and Repair)

► Show Figures

Figure 1

13 pages, 2244 KiB

Open AccessArticle

The Lack of Amyloidogenic Activity Is Persistent in Old WT and APP_swe/PS1ΔE9 Mouse Retinae

by Sandrine Joly, Léa Rodriguez and Vincent Pernet

Int. J. Mol. Sci. 2021, 22(21), 11344; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222111344 - 20 Oct 2021

Viewed by 2053

Abstract

We have previously reported that vision decline was not associated with amyloidogenesis processing in aging C57BL/6J wild-type (WT) mice and in a mouse model of Alzheimer’s disease, the APP_swe/PS1ΔE9 transgenic mouse model (APP/PS1). This conclusion was drawn using middle-aged (10–13 months old) mice. Here, we hypothesized that compared with hippocampal and cortical neurons, the weak amyloidogenic activity of retinal neurons may result in a detectable release of amyloid β (Aβ) only in aged mice, i.e., between 14 and 24 months of age. The aim of the present study was thus to follow potential activity changes in the amyloidogenic and nonamyloidogenic pathways of young (4 months) and old (20–24 months) WT and APP/PS1 mice. Our results showed that in spite of retinal activity loss reported by electroretinogram (ERG) recordings, the level of amyloid beta precursor protein (APP) and its derivatives did not significantly vary in the eyes of old vs. young mice. Strikingly, the ectopic expression of human APP_swe in APP/PS1 mice did not allow us to detect Aβ monomers at 23 months. In contrast, Aβ was observed in hippocampal and cortical tissues at this age but not at 4 months of life. In contrast, optic nerve transection-induced retinal ganglion cell injury significantly affected the level of retinal APP and the secretion of soluble APP alpha in the vitreous. Collectively, these results suggest that the amyloidogenic and nonamyloidogenic pathways are not involved in visual function decline in aging mice. In WT and APP/PS1 mice, it is proposed that retinal neurons do not have the capacity to secrete Aβ in contrast with other cortical and hippocampal neurons. Full article

(This article belongs to the Special Issue Retina Degeneration, Neuroprotection and Repair)

► Show Figures

Figure 1

19 pages, 3519 KiB

Open AccessArticle

Scaffold-Free Retinal Pigment Epithelium Microtissues Exhibit Increased Release of PEDF

by Abdullah Al-Ani, Derek Toms, Saud Sunba, Kayla Giles, Yacine Touahri, Carol Schuurmans and Mark Ungrin

Int. J. Mol. Sci. 2021, 22(21), 11317; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222111317 - 20 Oct 2021

Cited by 4 | Viewed by 2679

Abstract

The retinal pigmented epithelium (RPE) plays a critical role in photoreceptor survival and function. RPE deficits are implicated in a wide range of diseases that result in vision loss, including age-related macular degeneration (AMD) and Stargardt disease, affecting millions worldwide. Subretinal delivery of RPE cells is considered a promising avenue for treatment, and encouraging results from animal trials have supported recent progression into the clinic. However, the limited survival and engraftment of transplanted RPE cells delivered as a suspension continues to be a major challenge. While RPE delivery as epithelial sheets exhibits improved outcomes, this comes at the price of increased complexity at both the production and transplant stages. In order to combine the benefits of both approaches, we have developed size-controlled, scaffold-free RPE microtissues (RPE-µTs) that are suitable for scalable production and delivery via injection. RPE-µTs retain key RPE molecular markers, and interestingly, in comparison to conventional monolayer cultures, they show significant increases in the transcription and secretion of pigment-epithelium-derived factor (PEDF), which is a key trophic factor known to enhance the survival and function of photoreceptors. Furthermore, these microtissues readily spread in vitro on a substrate analogous to Bruch’s membrane, suggesting that RPE-µTs may collapse into a sheet upon transplantation. We anticipate that this approach may provide an alternative cell delivery system to improve the survival and integration of RPE transplants, while also retaining the benefits of low complexity in production and delivery. Full article

(This article belongs to the Special Issue Retina Degeneration, Neuroprotection and Repair)

► Show Figures

Figure 1

15 pages, 4088 KiB

Open AccessArticle

7,8-Dihydroxiflavone Protects Adult Rat Axotomized Retinal Ganglion Cells through MAPK/ERK and PI3K/AKT Activation

by Caridad Galindo-Romero, Beatriz Vidal-Villegas, Javier Asís-Martínez, Fernando Lucas-Ruiz, Alejandro Gallego-Ortega and Manuel Vidal-Sanz

Int. J. Mol. Sci. 2021, 22(19), 10896; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms221910896 - 08 Oct 2021

Cited by 11 | Viewed by 1799

Abstract

We analyze the 7,8-dihydroxyflavone (DHF)/TrkB signaling activation of two main intracellular pathways, mitogen-activated protein kinase (MAPK)/ERK and phosphatidylinositol 3 kinase (PI3K)/AKT, in the neuroprotection of axotomized retinal ganglion cells (RGCs). Methods: Adult albino Sprague-Dawley rats received left intraorbital optic nerve transection (IONT) and were divided in two groups. One group received daily intraperitoneal DHF (5 mg/kg) and another vehicle (1%DMSO in 0.9%NaCl) from one day before IONT until processing. Additional intact rats were employed as control (n = 4). At 1, 3 or 7 days (d) after IONT, phosphorylated (p)AKT, p-MAPK, and non-phosphorylated AKT and MAPK expression levels were analyzed in the retina by Western blotting (n = 4/group). Radial sections were also immunodetected for the above-mentioned proteins, and for Brn3a and vimentin to identify RGCs and Müller cells (MCs), respectively (n = 3/group). Results: IONT induced increased levels of p-MAPK and MAPK at 3d in DHF- or vehicle-treated retinas and at 7d in DHF-treated retinas. IONT induced a fast decrease in AKT in retinas treated with DHF or vehicle, with higher levels of phosphorylation in DHF-treated retinas at 7d. In intact retinas and vehicle-treated groups, no p-MAPK or MAPK expression in RGCs was observed. In DHF- treated retinas p-MAPK and MAPK were expressed in the ganglion cell layer and in the RGC nuclei 3 and 7d after IONT. AKT was observed in intact and axotomized RGCs, but the signal intensity of p-AKT was stronger in DHF-treated retinas. Finally, MCs expressed higher quantities of both MAPK and AKT at 3d in both DHF- and vehicle-treated retinas, and at 7d the phosphorylation of p-MAPK was higher in DHF-treated groups. Conclusions: Phosphorylation and increased levels of AKT and MAPK through MCs and RGCs in retinas after DHF-treatment may be responsible for the increased and long-lasting RGC protection afforded by DHF after IONT. Full article

(This article belongs to the Special Issue Retina Degeneration, Neuroprotection and Repair)

► Show Figures

Figure 1

21 pages, 6660 KiB

Open AccessArticle

Transplantation of Human Induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelium in a Swine Model of Geographic Atrophy

by Anna Duarri, Eduardo Rodríguez-Bocanegra, Gema Martínez-Navarrete, Marc Biarnés, Miriam García, Lucía Lee Ferraro, Bernd Kuebler, Begoña Aran, Elisabeth Izquierdo, Eli Aguilera-Xiol, Ricardo P. Casaroli-Marano, Esteve Trias, Eduardo Fernandez, Ángel Raya, Anna Veiga and Jordi Monés

Int. J. Mol. Sci. 2021, 22(19), 10497; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms221910497 - 28 Sep 2021

Cited by 11 | Viewed by 4156

Abstract

Background: The aim of this study was to test the feasibility and safety of subretinal transplantation of human induced pluripotent stem cell (hiPSC)-derived retinal pigment epithelium (RPE) cells into the healthy margins and within areas of degenerative retina in a swine model of geographic atrophy (GA). Methods: Well-delimited selective outer retinal damage was induced by subretinal injection of NaIO₃ into one eye in minipigs (n = 10). Thirty days later, a suspension of hiPSC-derived RPE cells expressing green fluorescent protein was injected into the subretinal space, into the healthy margins, and within areas of degenerative retina. In vivo follow-up was performed by multimodal imaging. Post-mortem retinas were analyzed by immunohistochemistry and histology. Results: In vitro differentiated hiPSC-RPE cells showed a typical epithelial morphology, expressed RPE-related genes, and had phagocytic ability. Engrafted hiPSC-RPE cells were detected in 60% of the eyes, forming mature epithelium in healthy retina extending towards the border of the atrophy. Histological analysis revealed RPE interaction with host photoreceptors in the healthy retina. Engrafted cells in the atrophic zone were found in a patchy distribution but failed to form an epithelial-like layer. Conclusions: These results might support the use of hiPSC-RPE cells to treat atrophic GA by providing a housekeeping function to aid the overwhelmed remnant RPE, which might improve its survival and therefore slow down the progression of GA. Full article

(This article belongs to the Special Issue Retina Degeneration, Neuroprotection and Repair)

► Show Figures

Figure 1

11 pages, 3314 KiB

Open AccessArticle

LED-Induced Microglial Activation and Rise in Caspase3 Suggest a Reorganization in the Retina

by Boglárka Balogh, Gergely Szarka, Ádám J. Tengölics, Gyula Hoffmann, Béla Völgyi and Tamás Kovács-Öller

Int. J. Mol. Sci. 2021, 22(19), 10418; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms221910418 - 27 Sep 2021

Cited by 2 | Viewed by 2174

Abstract

Vision is our primary sense as the human eye is the gateway for more than 65% of information reaching the human brain. Today’s increased exposure to different wavelengths and intensities of light from light emitting diode (LED) sources could induce retinal degeneration and accompanying neuronal cell death. Damage induced by chronic phototoxic reactions occurring in the retina accumulates over years and it has been suggested as being responsible for the etiology of many debilitating ocular conditions. In this work, we examined how LED stimulation affects vision by monitoring changes in the expression of death and survival factors as well as microglial activation in LED-induced damage (LID) of the retinal tissue. We found an LED-exposure-induced increase in the mRNA levels of major apoptosis-related markers BAX, Bcl-2, and Caspase-3 and accompanying widespread microglial and Caspase-3 activation. Everyday LED light exposure was accounted for in all the described changes in the retinal tissue of mice in this study, indicating that overuse of non-filtered direct LED light can have detrimental effects on the human retina as well. Full article

(This article belongs to the Special Issue Retina Degeneration, Neuroprotection and Repair)

► Show Figures

Figure 1

11 pages, 2763 KiB

Open AccessArticle

Short- and Long-Term Study of the Impact of Focal Blue Light-Emitting Diode-Induced Phototoxicity in Adult Albino Rats

by Juan A. Miralles de Imperial-Ollero, Alejandro Gallego-Ortega, María Norte-Muñoz, Johnny Di Pierdomenico, José Manuel Bernal-Garro, Francisco J. Valiente-Soriano and Manuel Vidal-Sanz

Int. J. Mol. Sci. 2021, 22(18), 9742; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22189742 - 09 Sep 2021

Cited by 5 | Viewed by 1838

Abstract

Background: In adult rats we study the short- and long-term effects of focal blue light-emitting diode (LED)-induced phototoxicity (LIP) on retinal thickness and Iba-1⁺ activation. Methods: The left eyes of previously dark-adapted Sprague Dawley (SD) rats were photoexposed to a blue LED (20 s, 200 lux). In vivo longitudinal monitoring of retinal thickness, fundus images, and optical retinal sections was performed from 1 to 30 days (d) after LIP with SD-OCT. Ex vivo, we analysed the population of S-cone and Iba-1⁺ cells within a predetermined fixed-size circular area (PCA) centred on the lesion. Results: LIP resulted in a circular focal lesion readily identifiable in vivo by fundus examination, which showed within the PCAs a progressive thinning of the outer retinal layer, and a diminution of the S-cone population to 19% by 30 d. In parallel to S-cone loss, activated Iba-1⁺ cells delineated the lesioned area and acquired an ameboid morphology with peak expression at 3 d after LIP. Iba-1⁺ cells adopted a more relaxed-branched morphology at 7 d and by 14–30 d their morphology was fully branched. Conclusion: LIP caused a progressive reduction of the outer retina with loss of S cones and a parallel dynamic activation of microglial cells in the lesioned area. Full article

(This article belongs to the Special Issue Retina Degeneration, Neuroprotection and Repair)

► Show Figures

Figure 1

29 pages, 10953 KiB

Open AccessArticle

Retinal Molecular Changes Are Associated with Neuroinflammation and Loss of RGCs in an Experimental Model of Glaucoma

by José A. Fernández-Albarral, Juan J. Salazar, Rosa de Hoz, Eva M. Marco, Beatriz Martín-Sánchez, Elena Flores-Salguero, Elena Salobrar-García, Inés López-Cuenca, Vicente Barrios-Sabador, Marcelino Avilés-Trigueros, Francisco J. Valiente-Soriano, Juan A. Miralles de Imperial-Ollero, Manuel Vidal-Sanz, Alberto Triviño, José M. Ramírez, Meritxell López-Gallardo and Ana I. Ramírez

Int. J. Mol. Sci. 2021, 22(4), 2066; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22042066 - 19 Feb 2021

Cited by 26 | Viewed by 3056

Abstract

Signaling mediated by cytokines and chemokines is involved in glaucoma-associated neuroinflammation and in the damage of retinal ganglion cells (RGCs). Using multiplexed immunoassay and immunohistochemical techniques in a glaucoma mouse model at different time points after ocular hypertension (OHT), we analyzed (i) the expression of pro-inflammatory cytokines, anti-inflammatory cytokines, BDNF, VEGF, and fractalkine; and (ii) the number of Brn3a+ RGCs. In OHT eyes, there was an upregulation of (i) IFN-γ at days 3, 5, and 15; (ii) IL-4 at days 1, 3, 5, and 7 and IL-10 at days 3 and 5 (coinciding with downregulation of IL1-β at days 1, 5, and 7); (iii) IL-6 at days 1, 3, and 5; (iv) fractalkine and VEGF at day 1; and (v) BDNF at days 1, 3, 7, and 15. In contralateral eyes, there were (i) an upregulation of IL-1β at days 1 and 3 and a downregulation at day 7, coinciding with the downregulation of IL4 at days 3 and 5 and the upregulation at day 7; (ii) an upregulation of IL-6 at days 1, 5, and 7 and a downregulation at 15 days; (iii) an upregulation of IL-10 at days 3 and 7; and (iv) an upregulation of IL-17 at day 15. In OHT eyes, there was a reduction in the Brn3a+ RGCs number at days 3, 5, 7, and 15. OHT changes cytokine levels in both OHT and contralateral eyes at different time points after OHT induction, confirming the immune system involvement in glaucomatous neurodegeneration. Full article

(This article belongs to the Special Issue Retina Degeneration, Neuroprotection and Repair)

► Show Figures

Figure 1

Review

Jump to: Research

29 pages, 474 KiB

Open AccessReview

The Next Generation of Molecular and Cellular Therapeutics for Inherited Retinal Disease

by Luis A. Martinez Velazquez and Brian G. Ballios

Int. J. Mol. Sci. 2021, 22(21), 11542; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222111542 - 26 Oct 2021

Cited by 8 | Viewed by 2982

Abstract

Inherited retinal degenerations (IRDs) are a diverse group of conditions that are often characterized by the loss of photoreceptors and blindness. Recent innovations in molecular biology and genomics have allowed us to identify the causative defects behind these dystrophies and to design therapeutics that target specific mechanisms of retinal disease. Recently, the FDA approved the first in vivo gene therapy for one of these hereditary blinding conditions. Current clinical trials are exploring new therapies that could provide treatment for a growing number of retinal dystrophies. While the field has had early success with gene augmentation strategies for treating retinal disease based on loss-of-function mutations, many novel approaches hold the promise of offering therapies that span the full spectrum of causative mutations and mechanisms. Here, we provide a comprehensive review of the approaches currently in development including a discussion of retinal neuroprotection, gene therapies (gene augmentation, gene editing, RNA modification, optogenetics), and regenerative stem or precursor cell-based therapies. Our review focuses on technologies that are being developed for clinical translation or are in active clinical trials and discusses the advantages and limitations for each approach. Full article

(This article belongs to the Special Issue Retina Degeneration, Neuroprotection and Repair)

20 pages, 3802 KiB

Open AccessReview

The Future of Stem Cells and Their Derivates in the Treatment of Glaucoma. A Critical Point of View

by Simona Delia Nicoară, Ioana Brie, Ancuța Jurj and Olga Sorițău

Int. J. Mol. Sci. 2021, 22(20), 11077; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222011077 - 14 Oct 2021

Cited by 7 | Viewed by 4064

Abstract

This review focuses on the clinical translation of preclinical studies, especially those that have used stem cells in the treatment of glaucoma, with an emphasis on optic nerve regeneration. The studies referred to in the review aim to treat optic nerve atrophy, while cell therapies targeting other sites in the eye, such as the trabecular meshwork, have not been addressed. Such complex and varied pathophysiological mechanisms that lead to glaucoma may explain the fact that although stem cells have a high capacity of neuronal regeneration, the treatments performed did not have the expected results and the promise offered by animal studies was not achieved. By analyzing the facts associated with failure, important lessons are to be learned: the type of stem cells that are used, the route of administration, the selection of patients eligible for these treatments, additional therapies that support stem cells transplantation and their mode of action, methods of avoiding the host’s immune response. Many of these problems could be solved using exosomes (EV), but also miRNA, which allows more targeted approaches with minimal side effects. Full article

(This article belongs to the Special Issue Retina Degeneration, Neuroprotection and Repair)

► Show Figures

Figure 1

20 pages, 749 KiB

Open AccessReview

Looking for In Vitro Models for Retinal Diseases

by Margherita Alfonsetti, Vanessa Castelli, Michele d’Angelo, Elisabetta Benedetti, Marcello Allegretti, Barbara Barboni and Annamaria Cimini

Int. J. Mol. Sci. 2021, 22(19), 10334; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms221910334 - 25 Sep 2021

Cited by 8 | Viewed by 4205

Abstract

Retina is a layered structure of the eye, composed of different cellular components working together to produce a complex visual output. Because of its important role in visual function, retinal pathologies commonly represent the main causes of visual injury and blindness in the industrialized world. It is important to develop in vitro models of retinal diseases to use them in first screenings before translating in in vivo experiments and clinics. For this reason, it is important to develop bidimensional (2D) models that are more suitable for drug screening and toxicological studies and tridimensional (3D) models, which can replicate physiological conditions, for investigating pathological mechanisms leading to visual loss. This review provides an overview of the most common retinal diseases, relating to in vivo models, with a specific focus on alternative 2D and 3D in vitro models that can replicate the different cellular and matrix components of retinal layers, as well as injury insults that induce retinal disease and loss of the visual function. Full article

(This article belongs to the Special Issue Retina Degeneration, Neuroprotection and Repair)

► Show Figures

Figure 1

21 pages, 2504 KiB

Open AccessReview

Risk Factors for Retinal Ganglion Cell Distress in Glaucoma and Neuroprotective Potential Intervention

by Stefania Vernazza, Francesco Oddone, Sara Tirendi and Anna Maria Bassi

Int. J. Mol. Sci. 2021, 22(15), 7994; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22157994 - 27 Jul 2021

Cited by 29 | Viewed by 4235

Abstract

Retinal ganglion cells (RGCs) are a population of neurons of the central nervous system (CNS) extending with their soma to the inner retina and with their axons to the optic nerve. Glaucoma represents a group of neurodegenerative diseases where the slow progressive death of RGCs results in a permanent loss of vision. To date, although Intra Ocular Pressure (IOP) is considered the main therapeutic target, the precise mechanisms by which RGCs die in glaucoma have not yet been clarified. In fact, Primary Open Angle Glaucoma (POAG), which is the most common glaucoma form, also occurs without elevated IOP. This present review provides a summary of some pathological conditions, i.e., axonal transport blockade, glutamate excitotoxicity and changes in pro-inflammatory cytokines along the RGC projection, all involved in the glaucoma cascade. Moreover, neuro-protective therapeutic approaches, which aim to improve RGC degeneration, have also been taken into consideration. Full article

(This article belongs to the Special Issue Retina Degeneration, Neuroprotection and Repair)

► Show Figures