Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

Journal Browser

Advanced Research in Retina 2.0

Special Issue Editors
Special Issue Information
Keywords
Related Special Issue
Published Papers

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (15 April 2024) | Viewed by 12624

Share This Special Issue

Special Issue Editors

Dr. Juan J. Salazar

E-Mail Website
Guest Editor

Instituto de Investigaciones Oftalmológicas Ramón Castroviejo, Departamento Oftalmología y ORL, Universidad Complutense de Madrid, 28040 Madrid, Spain
Interests: retina ganglion cell; intraocular pressure; nerve fibers; retinal; optical coherence tomography; trabeculectomy; glaucoma; anterior eye chamber; ophthalmology

Dr. José A. Fernández-Albarral

E-Mail Website
Guest Editor

Instituto de Investigaciones Oftalmológicas Ramón Castroviejo, Universidad Complutense de Madrid, 28040 Madrid, Spain
Interests: neurophysioly; central nervous system; neuronal and glial cells; neuroinflammation; therapeutical approaches
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The retina is one of the main structures of the eye and a fundamental part of the vision process. It is also part of the central nervous system (CNS), as it is an extension of the brain.

As a fundamental structure in the visual process, the retina is involved in several pathologies that affect vision and constitute one of the main causes of blindness in the world, including age-related macular degeneration, diabetic retinopathy, and glaucoma, among others. Therefore, advances in research into the pathogenic mechanisms of these diseases and their treatments could represent a major advance in the control of these retinal pathologies.

As part of the central nervous system, the retina can undergo pathological changes related to neurodegenerative processes such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), among others. Thanks to its accessibility and the development of non-invasive imaging techniques, the retina is now considered a biomarker for studying these neurodegenerative pathologies. Therefore, the study of the involvement of the retina in neurodegenerative pathologies, as well as the monitoring, through the retina, of their progression and possible treatments, could represent important advances in the future diagnosis and therapy of these neurodegenerative pathologies.

The Special Issue aims to provide a research platform for the collection of the latest original and review articles covering the pathogenic mechanisms of diverse retinal pathologies, innovative diagnostic techniques, and the development of new therapeutic strategies. It also includes articles investigating retinal alterations in neurodegenerative diseases (AD, PD, ALS, among others), the development of new diagnostic techniques using the retina, and the monitoring of new treatments through the retina.

Dr. Juan J. Salazar
Dr. José A. Fernández-Albarral
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

glaucoma
age-related macular degeneration
diabetic retinopathy
neurodegenerative diseases
diagnostic techniques
therapeutic strategies

Related Special Issue

Advanced Research in Retina in International Journal of Molecular Sciences (12 articles)

Published Papers (8 papers)

Download All Papers

Order results

Result details

Show export options Show export options

Select all

Export citation of selected articles as:

Research

Jump to: Review

25 pages, 4579 KiB

Open AccessArticle

Cilastatin as a Potential Anti-Inflammatory and Neuroprotective Treatment in the Management of Glaucoma

by Miguel A. Martínez-López, Sara Rubio-Casado, Diego San Felipe, Beatriz Martín-Sánchez, José A. Fernández-Albarral, Elena Salobrar-García, José A. Matamoros, José M. Ramírez, Rosa de Hoz, Juan J. Salazar, Eva M. Marco, Ana I. Ramírez, Alberto Lázaro and Meritxell López-Gallardo

Int. J. Mol. Sci. 2024, 25(6), 3115; https://doi.org/10.3390/ijms25063115 - 7 Mar 2024

Viewed by 1373

Abstract

Glaucoma is a neurodegenerative disease that causes blindness. In this study, we aimed to evaluate the protective role of cilastatin (CIL), generally used in the treatment of nephropathologies associated with inflammation, in an experimental mouse model based on unilateral (left) laser-induced ocular hypertension (OHT). Male Swiss mice were administered CIL daily (300 mg/kg, i.p.) two days before OHT surgery until sacrifice 3 or 7 days later. Intraocular Pressure (IOP), as well as retinal ganglion cell (RGC) survival, was registered, and the inflammatory responses of macroglial and microglial cells were studied via immunohistochemical techniques. Results from OHT eyes were compared to normotensive contralateral (CONTRA) and naïve control eyes considering nine retinal areas and all retinal layers. OHT successfully increased IOP values in OHT eyes but not in CONTRA eyes; CIL did not affect IOP values. Surgery induced a higher loss of RGCs in OHT eyes than in CONTRA eyes, while CIL attenuated this loss. Similarly, surgery increased macroglial and microglial activation in OHT eyes and to a lesser extent in CONTRA eyes; CIL prevented both macroglial and microglial activation in OHT and CONTRA eyes. Therefore, CIL arises as a potential effective strategy to reduce OHT-associated damage in the retina of experimental mice. Full article

(This article belongs to the Special Issue Advanced Research in Retina 2.0)

► Show Figures

Figure 1

16 pages, 2560 KiB

Open AccessArticle

RAR Inhibitors Display Photo-Protective and Anti-Inflammatory Effects in A2E Stimulated RPE Cells In Vitro through Non-Specific Modulation of PPAR or RXR Transactivation

by Valérie Fontaine, Thinhinane Boumedine, Elodie Monteiro, Mylène Fournié, Gendre Gersende, José-Alain Sahel, Serge Picaud, Stanislas Veillet, René Lafont, Mathilde Latil, Pierre J. Dilda and Serge Camelo

Int. J. Mol. Sci. 2024, 25(5), 3037; https://doi.org/10.3390/ijms25053037 - 6 Mar 2024

Viewed by 970

Abstract

N-retinylidene-N-retinylethanolamine (A2E) has been associated with age-related macular degeneration (AMD) physiopathology by inducing cell death, angiogenesis and inflammation in retinal pigmented epithelial (RPE) cells. It was previously thought that the A2E effects were solely mediated via the retinoic acid receptor (RAR)-α activation. However, this conclusion was based on experiments using the RAR “specific” antagonist RO-41-5253, which was found to also be a ligand and partial agonist of the peroxisome proliferator-activated receptor (PPAR)-γ. Moreover, we previously reported that inhibiting PPAR and retinoid X receptor (RXR) transactivation with norbixin also modulated inflammation and angiogenesis in RPE cells challenged in the presence of A2E. Here, using several RAR inhibitors, we deciphered the respective roles of RAR, PPAR and RXR transactivations in an in vitro model of AMD. We showed that BMS 195614 (a selective RAR-α antagonist) displayed photoprotective properties against toxic blue light exposure in the presence of A2E. BMS 195614 also significantly reduced the AP-1 transactivation and mRNA expression of the inflammatory interleukin (IL)-6 and vascular endothelial growth factor (VEGF) induced by A2E in RPE cells in vitro, suggesting a major role of RAR in these processes. Surprisingly, however, we showed that (1) Norbixin increased the RAR transactivation and (2) AGN 193109 (a high affinity pan-RAR antagonist) and BMS 493 (a pan-RAR inverse agonist), which are photoprotective against toxic blue light exposure in the presence of A2E, also inhibited PPARs transactivation and RXR transactivation, respectively. Therefore, in our in vitro model of AMD, several commercialized RAR inhibitors appear to be non-specific, and we propose that the phototoxicity and expression of IL-6 and VEGF induced by A2E in RPE cells operates through the activation of PPAR or RXR rather than by RAR transactivation. Full article

(This article belongs to the Special Issue Advanced Research in Retina 2.0)

► Show Figures

Figure 1

15 pages, 17109 KiB

Open AccessArticle

Ischemia-Reperfusion Increases TRPM7 Expression in Mouse Retinas

by Natalia Martínez-Gil, Oksana Kutsyr, Laura Fernández-Sánchez, Xavier Sánchez-Sáez, Henar Albertos-Arranz, Carla Sánchez-Castillo, Lorena Vidal-Gil, Nicolás Cuenca, Pedro Lax and Victoria Maneu

Int. J. Mol. Sci. 2023, 24(22), 16068; https://doi.org/10.3390/ijms242216068 - 8 Nov 2023

Cited by 1 | Viewed by 1171

Abstract

Ischemia is the main cause of cell death in retinal diseases such as vascular occlusions, diabetic retinopathy, glaucoma, or retinopathy of prematurity. Although excitotoxicity is considered the primary mechanism of cell death during an ischemic event, antagonists of glutamatergic receptors have been unsuccessful in clinical trials with patients suffering ischemia or stroke. Our main purpose was to analyze if the transient receptor potential channel 7 (TRPM7) could contribute to retinal dysfunction in retinal pathologies associated with ischemia. By using an experimental model of acute retinal ischemia, we analyzed the changes in retinal function by electroretinography and the changes in retinal morphology by optical coherence tomography (OCT) and OCT-angiography (OCTA). Immunohistochemistry was performed to assess the pattern of TRPM7 and its expression level in the retina. Our results show that ischemia elicited a decrease in retinal responsiveness to light stimuli along with reactive gliosis and a significant increase in the expression of TRPM7 in Müller cells. TRPM7 could emerge as a new drug target to be explored in retinal pathologies associated with ischemia. Full article

(This article belongs to the Special Issue Advanced Research in Retina 2.0)

► Show Figures

Figure 1

23 pages, 6948 KiB

Open AccessArticle

Intravitreal Administration of Retinal Organoids-Derived Exosomes Alleviates Photoreceptor Degeneration in Royal College of Surgeons Rats by Targeting the Mitogen-Activated Protein Kinase Pathway

by Jung Woo Han, Hun Soo Chang, Jin Young Yang, Han Sol Choi, Hyo Song Park, Hyoung Oh Jun, Ji Hye Choi, Sun-Sook Paik, Kyung Hwun Chung, Hee Jeong Shin, Seungyeon Nam, Ji-Hye Son, Si Hyung Lee, Eun Jung Lee, Kyoung Yul Seo, Jungmook Lyu, Jin Woo Kim, In-Beom Kim and Tae Kwann Park

Int. J. Mol. Sci. 2023, 24(15), 12068; https://doi.org/10.3390/ijms241512068 - 27 Jul 2023

Cited by 3 | Viewed by 2333

Abstract

Increasing evidence suggests that exosomes are involved in retinal cell degeneration, including their insufficient release; hence, they have become important indicators of retinopathies. The exosomal microRNA (miRNA), in particular, play important roles in regulating ocular and retinal cell functions, including photoreceptor maturation, maintenance, and visual function. Here, we generated retinal organoids (ROs) from human induced pluripotent stem cells that differentiated in a conditioned medium for 60 days, after which exosomes were extracted from ROs (Exo-ROs). Subsequently, we intravitreally injected the Exo-RO solution into the eyes of the Royal College of Surgeons (RCS) rats. Intravitreal Exo-RO administration reduced photoreceptor apoptosis, prevented outer nuclear layer thinning, and preserved visual function in RCS rats. RNA sequencing and miRNA profiling showed that exosomal miRNAs are mainly involved in the mitogen-activated protein kinase (MAPK) signaling pathway. In addition, the expression of MAPK-related genes and proteins was significantly decreased in the Exo-RO-treated group. These results suggest that Exo-ROs may be a potentially novel strategy for delaying retinal degeneration by targeting the MAPK signaling pathway. Full article

(This article belongs to the Special Issue Advanced Research in Retina 2.0)

► Show Figures

Figure 1

17 pages, 2328 KiB

Open AccessArticle

PRGF Membrane with Tailored Optical Properties Preserves the Cytoprotective Effect of Plasma Rich in Growth Factors: In Vitro Model of Retinal Pigment Epithelial Cells

by Eduardo Anitua, Francisco Muruzabal, María de la Fuente, Susana Del Olmo-Aguado, Mohammad H. Alkhraisat and Jesús Merayo-Lloves

Int. J. Mol. Sci. 2023, 24(13), 11195; https://doi.org/10.3390/ijms241311195 - 7 Jul 2023

Cited by 1 | Viewed by 1016

Abstract

The present study evaluates the ability of a novel plasma rich in growth factors (PRGF) membrane with improved optical properties to reduce oxidative stress in retinal pigment epithelial cells (ARPE-19 cells) exposed to blue light. PRGF was obtained from three healthy donors and divided into four main groups: (i) PRGF membrane (M-PRGF), (ii) PRGF supernatant (S-PRGF), (iii) platelet-poor plasma (PPP) membrane diluted 50% with S-PRGF (M-PPP 50%), and (iv) M-PPP 50% supernatant (S-PPP 50%). ARPE-19 cells were exposed to blue light and then incubated with the different PRGF-derived formulations or control for 24 and 48 h under blue light exposure. Mitochondrial and cell viability, reactive oxygen species (ROS) production, and heme oxygenase-1 (HO-1) and ZO-1 expression were evaluated. Mitochondrial viability and cell survival were significantly increased after treatment with the different PRGF-derived formulations. ROS synthesis and HO-1 expression were significantly reduced after cell treatment with any of the PRGF-derived formulations. Furthermore, the different PRGF-derived formulations significantly increased ZO-1 expression in ARPE-19 exposed to blue light. The new PRGF membrane with improved optical properties and its supernatant (M-PPP 50% and S-PPP 50%) protected and reversed blue light-induced oxidative stress in ARPE-19 cells at levels like those of a natural PRGF membrane and its supernatant. Full article

(This article belongs to the Special Issue Advanced Research in Retina 2.0)

► Show Figures

Figure 1

14 pages, 3961 KiB

Open AccessArticle

Activin A Limits VEGF-Induced Permeability via VE-PTP

by Basma Baccouche, Lina Lietuvninkas and Andrius Kazlauskas

Int. J. Mol. Sci. 2023, 24(10), 8698; https://doi.org/10.3390/ijms24108698 - 12 May 2023

Cited by 1 | Viewed by 1406

Abstract

The clinical success of neutralizing vascular endothelial growth factor (VEGF) has unequivocally identified VEGF as a driver of retinal edema that underlies a variety of blinding conditions. VEGF is not the only input that is received and integrated by the endothelium. For instance, the permeability of blood vessels is also regulated by the large and ubiquitously expressed transforming growth factor beta (TGF-β) family. In this project, we tested the hypothesis that members of the TGF-β family influence the VEGF-mediated control of the endothelial cell barrier. To this end, we compared the effect of bone morphogenetic protein-9 (BMP-9), TGF-β1, and activin A on the VEGF-driven permeability of primary human retinal endothelial cells. While BMP-9 and TGF-β1 had no effect on VEGF-induced permeability, activin A limited the extent to which VEGF relaxed the barrier. This activin A effect was associated with the reduced activation of VEGFR2 and its downstream effectors and an increased expression of vascular endothelial tyrosine phosphatase (VE-PTP). Attenuating the expression or activity of VE-PTP overcame the effect of activin A. Taken together, these observations indicate that the TGF-β superfamily governed VEGF-mediated responsiveness in a ligand-specific manner. Furthermore, activin A suppressed the responsiveness of cells to VEGF, and the underlying mechanism involved the VE-PTP-mediated dephosphorylation of VEGFR2. Full article

(This article belongs to the Special Issue Advanced Research in Retina 2.0)

► Show Figures

Figure 1

23 pages, 7397 KiB

Open AccessArticle

Transcriptomic Changes Predict Metabolic Alterations in LC3 Associated Phagocytosis in Aged Mice

by Anuradha Dhingra, John W. Tobias, Nancy J. Philp and Kathleen Boesze-Battaglia

Int. J. Mol. Sci. 2023, 24(7), 6716; https://doi.org/10.3390/ijms24076716 - 4 Apr 2023

Viewed by 1870

Abstract

LC3b (Map1lc3b) plays an essential role in canonical autophagy and is one of several components of the autophagy machinery that mediates non-canonical autophagic functions. Phagosomes are often associated with lipidated LC3b to promote phagosome maturation in a process called LC3-associated phagocytosis (LAP). Specialized phagocytes, such as mammary epithelial cells, retinal pigment epithelial (RPE) cells, and sertoli cells, utilize LAP for optimal degradation of phagocytosed material, including debris. In the visual system, LAP is critical to maintain retinal function, lipid homeostasis, and neuroprotection. In a mouse model of retinal lipid steatosis-mice lacking LC3b (LC3b^−/−), we observed increased lipid deposition, metabolic dysregulation, and enhanced inflammation. Herein, we present a non-biased approach to determine if loss of LAP mediated processes modulate the expression of various genes related to metabolic homeostasis, lipid handling, and inflammation. A comparison of the RPE transcriptome of WT and LC3b^−/− mice revealed 1533 DEGs, with ~73% upregulated and 27% downregulated. Enriched gene ontology (GO) terms included inflammatory response (upregulated DEGs), fatty acid metabolism, and vascular transport (downregulated DEGs). Gene set enrichment analysis (GSEA) identified 34 pathways; 28 were upregulated (dominated by inflammation/related pathways) and 6 were downregulated (dominated by metabolic pathways). Analysis of additional gene families identified significant differences for genes in the solute carrier family, RPE signature genes, and genes with a potential role in age-related macular degeneration. These data indicate that loss of LC3b induces robust changes in the RPE transcriptome contributing to lipid dysregulation and metabolic imbalance, RPE atrophy, inflammation, and disease pathophysiology. Full article

(This article belongs to the Special Issue Advanced Research in Retina 2.0)

► Show Figures

Figure 1

Review

Jump to: Research

28 pages, 546 KiB

Open AccessReview

Retinal Alterations Predict Early Prodromal Signs of Neurodegenerative Disease

by Fabio Casciano, Enrico Zauli, Claudio Celeghini, Lorenzo Caruso, Arianna Gonelli, Giorgio Zauli and Angela Pignatelli

Int. J. Mol. Sci. 2024, 25(3), 1689; https://doi.org/10.3390/ijms25031689 - 30 Jan 2024

Viewed by 1596

Abstract

Neurodegenerative diseases are an increasingly common group of diseases that occur late in life with a significant impact on personal, family, and economic life. Among these, Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the major disorders that lead to mild to severe cognitive and physical impairment and dementia. Interestingly, those diseases may show onset of prodromal symptoms early after middle age. Commonly, the evaluation of these neurodegenerative diseases is based on the detection of biomarkers, where functional and structural magnetic resonance imaging (MRI) have shown a central role in revealing early or prodromal phases, although it can be expensive, time-consuming, and not always available. The aforementioned diseases have a common impact on the visual system due to the pathophysiological mechanisms shared between the eye and the brain. In Parkinson’s disease, α-synuclein deposition in the retinal cells, as well as in dopaminergic neurons of the substantia nigra, alters the visual cortex and retinal function, resulting in modifications to the visual field. Similarly, the visual cortex is modified by the neurofibrillary tangles and neuritic amyloid β plaques typically seen in the Alzheimer’s disease brain, and this may reflect the accumulation of these biomarkers in the retina during the early stages of the disease, as seen in postmortem retinas of AD patients. In this light, the ophthalmic evaluation of retinal neurodegeneration could become a cost-effective method for the early diagnosis of those diseases, overcoming the limitations of functional and structural imaging of the deep brain. This analysis is commonly used in ophthalmic practice, and interest in it has risen in recent years. This review will discuss the relationship between Alzheimer’s disease and Parkinson’s disease with retinal degeneration, highlighting how retinal analysis may represent a noninvasive and straightforward method for the early diagnosis of these neurodegenerative diseases. Full article

(This article belongs to the Special Issue Advanced Research in Retina 2.0)

► Show Figures

Journal Menu

Journal Browser

Advanced Research in Retina 2.0

Share This Special Issue

Special Issue Editors

Special Issue Information

Keywords

Related Special Issue

Published Papers (8 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI