Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

Journal Browser

Molecular Mechanisms of Retinal Degeneration and How to Avoid It—2nd Edition

Special Issue Editors
Special Issue Information
Keywords
Benefits of Publishing in a 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 (20 January 2025) | Viewed by 14602

Share This Special Issue

Special Issue Editors

Prof. Dr. Tamás Kovács-Öller

E-Mail Website
Guest Editor

Szentagothai Research Centre, University of Pécs, 7624 Pécs, Hungary
Interests: gap junction; retina; neurobiology; patch clamp; calcium-imaging; vision
Special Issues, Collections and Topics in MDPI journals

Dr. Bela Volgyi

E-Mail Website
Guest Editor

Retinal Neurobiology Rresearch Group, Pécsi Tudományegyetem, 7622 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 Colleagues,

Vision is the most important sensory modality in vertebrates in general and as such, it is the most feared sense to lose. The retina is the site for visual perception and we desperately need new tools and advanced therapeutic regimens to avoid retinal regeneration or at least slow down ongoing vision deteriorating diseases including glaucoma, diabetic retinopathy, age-related macular degeneration, myopia, retinal vascular disease, traumatic brain injuries, and many others.

Most cell types in the retina are involved in the deterioration process and thus suffer from these diseases including the neurons (ganglion cells, amacrine cells, bipolar cells, horizontal cells, and photoreceptors) as well non-neuronal (astrocytes, microglia, and Müller cells) cells. Comprehending the molecular mechanisms by which these diseases alter their function is crucial. Our special issue aims to widen our knowledge to help understand the disease phenotypes at all investigation levels since there is still a lack of information in identifying potential targets for regeneration or at least help retinal survival and restore vision.

We are looking forward to receiving your original research manuscripts or reviews.

Prof. Dr. Tamás Kovács-Öller
Dr. Bela Volgyi
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

retinal degeneration
retina
disease
glaucoma
diabetic retinopathy
age-related macular degeneration
myopia
retinal vascular disease
traumatic brain injury
molecular mechanisms

Benefits of Publishing in a Special Issue

Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
Reprint: MDPI Books provides the opportunity to republish successful Special Issues in book format, both online and in print.

Further information on MDPI's Special Issue policies can be found here.

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

24 pages, 1646 KiB

Open AccessArticle

The Impact of ARMS2 (rs10490924), VEGFA (rs3024997), TNFRSF1B (rs1061622), TNFRSF1A (rs4149576), and IL1B1 (rs1143623) Polymorphisms and Serum Levels on Age-Related Macular Degeneration Development and Therapeutic Responses

by Dzastina Cebatoriene, Alvita Vilkeviciute, Greta Gedvilaite-Vaicechauskiene, Monika Duseikaite, Akvile Bruzaite, Loresa Kriauciuniene, Dalia Zaliuniene and Rasa Liutkeviciene

Int. J. Mol. Sci. 2024, 25(17), 9750; https://doi.org/10.3390/ijms25179750 - 9 Sep 2024

Cited by 3 | Viewed by 1391

Abstract

Age-related macular degeneration (AMD) is a major global health problem as it is the leading cause of irreversible loss of central vision in the aging population. Anti-vascular endothelial growth factor (anti-VEGF) therapies are effective but do not respond optimally in all patients. This study investigates the genetic factors associated with susceptibility to AMD and response to treatment, focusing on key polymorphisms in the ARMS2 (rs10490924), IL1B1 (rs1143623), TNFRSF1B (rs1061622), TNFRSF1A (rs4149576), VEGFA (rs3024997), ARMS2, IL1B1, TNFRSF1B, TNFRSF1A, and VEGFA serum levels in AMD development and treatment efficacy. This study examined the associations of specific genetic polymorphisms and serum protein levels with exudative and early AMD and the response to anti-VEGF treatment. The AA genotype of VEGFA (rs3024997) was significantly associated with a 20-fold reduction in the odds of exudative AMD compared to the GG + GA genotypes. Conversely, the TT genotype of ARMS2 (rs10490924) was linked to a 4.2-fold increase in the odds of exudative AMD compared to GG + GT genotypes. In females, each T allele of ARMS2 increased the odds by 2.3-fold, while in males, the TT genotype was associated with a 5-fold increase. Lower serum IL1B levels were observed in the exudative AMD group compared to the controls. Early AMD patients had higher serum TNFRSF1B levels than controls, particularly those with the GG genotype of TNFRSF1B rs1061622. Exudative AMD patients with the CC genotype of TNFRSF1A rs4149576 had lower serum TNFRSF1A levels compared to the controls. Visual acuity (VA) analysis showed that non-responders had better baseline VA than responders but experienced decreased VA after treatment, whereas responders showed improvement. Central retinal thickness (CRT) reduced significantly in responders after treatment and was lower in responders compared to non-responders after treatment. The T allele of TNFRSF1B rs1061622 was associated with a better response to anti-VEGF treatment under both dominant and additive genetic models. These findings highlight significant genetic and biochemical markers associated with AMD and treatment response. This study found that the VEGFA rs3024997 AA genotype reduces the odds of exudative AMD, while the ARMS2 rs10490924 TT genotype increases it. Lower serum IL1B levels and variations in TNFRSF1B and TNFRSF1A levels were linked to AMD. The TNFRSF1B rs1061622 T allele was associated with better anti-VEGF treatment response. These markers could potentially guide risk assessment and personalized treatment for AMD. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Retinal Degeneration and How to Avoid It—2nd Edition)

► Show Figures

Figure 1

21 pages, 4109 KiB

Open AccessArticle

Effects of Fucoidans on Activated Retinal Microglia

by Philipp Dörschmann, Florentine Hunger, Hannah Schroth, Sibei Chen, Georg Kopplin, Johann Roider and Alexa Klettner

Int. J. Mol. Sci. 2024, 25(11), 6018; https://doi.org/10.3390/ijms25116018 - 30 May 2024

Cited by 1 | Viewed by 1528

Abstract

Sulfated marine polysaccharides, so-called fucoidans, have been shown to exhibit anti-inflammatory and immunomodulatory activities in retinal pigment epithelium (RPE). In this study, we tested the effects of different fucoidans (and of fucoidan-treated RPE cells) on retinal microglia to investigate whether its anti-inflammatory effect can be extrapolated to the innate immune cells of the retina. In addition, we tested whether fucoidan treatment influenced the anti-inflammatory effect of RPE cells on retinal microglia. Three fucoidans were tested (FVs from Fucus vesiculosus, Fuc1 and FucBB04 from Laminaria hyperborea) as well as the supernatant of primary porcine RPE treated with fucoidans for their effects on inflammatory activated (using lipopolysaccharide, LPS) microglia cell line SIM-A9 and primary porcine retinal microglia. Cell viability was detected with a tetrazolium assay (MTT), and morphology by Coomassie staining. Secretion of tumor necrosis factor alpha (TNFα), interleukin 1 beta (IL1β) and interleukin 8 (IL8) was detected with ELISA, gene expression (NOS2 (Nitric oxide synthase 2), and CXCL8 (IL8)) with qPCR. Phagocytosis was detected with a fluorescence assay. FucBB04 and FVs slightly reduced the viability of SIM-A9 and primary microglia, respectively. Treatment with RPE supernatants increased the viability of LPS-treated primary microglia. FVs and FucBB04 reduced the size of LPS-activated primary microglia, indicating an anti-inflammatory phenotype. RPE supernatant reduced the size of LPS-activated SIM-A9 cells. Proinflammatory cytokine secretion and gene expression in SIM-A9, as well as primary microglia, were not significantly affected by fucoidans, but RPE supernatants reduced the secretion of LPS-induced proinflammatory cytokine secretion in SIM-A9 and primary microglia. The phagocytosis ability of primary microglia was reduced by FucBB04. In conclusion, fucoidans exhibited only modest effects on inflammatorily activated microglia by maintaining their cell size under stimulation, while the anti-inflammatory effect of RPE cells on microglia irrespective of fucoidan treatment could be confirmed, stressing the role of RPE in regulating innate immunity in the retina. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Retinal Degeneration and How to Avoid It—2nd Edition)

► Show Figures

Figure 1

Review

Jump to: Research

15 pages, 850 KiB

Open AccessReview

Eyes Are the Windows to the Soul: Reviewing the Possible Use of the Retina to Indicate Traumatic Brain Injury

by Loretta Péntek, Gergely Szarka, Liliana Ross, Boglárka Balogh, Ildikó Telkes, Béla Völgyi and Tamás Kovács-Öller

Int. J. Mol. Sci. 2025, 26(11), 5171; https://doi.org/10.3390/ijms26115171 - 28 May 2025

Viewed by 200

Abstract

Traumatic brain injury (TBI) induces complex molecular and cellular responses, often leading to vision deterioration and potential mortality. Current objective diagnostic methods are limited, necessitating the development of novel tools to assess disease severity. This review focuses on the retina, a readily approachable part of the central nervous system (CNS), as a potential indicator of TBI. We conduct a targeted database search and employ a blinded scoring system, incorporating both human and artificial intelligence (AI) assessments, to identify relevant articles. We then perform a detailed analysis to elucidate the molecular pathways and cellular changes in the retina following TBI. Recent findings highlight the involvement of key molecular markers, such as ionized calcium-binding adapter molecule 1 (IBA1), phosphorylated tau, glial fibrillary acidic protein (GFAP), and various cytokines (IL-1β, IL-6, and TNF). Additionally, the roles of oxidative stress, reactive oxygen species (ROS), and blood–retina barrier (BRB) disruption are explored. Based on these findings, we hypothesize that alterations in these molecular pathways and cellular components, particularly microglia, can serve as direct indicators of brain health and TBI severity. Recent technological advancements in retinal imaging now allow for a direct assessment of retinal cells, including microglia, and related inflammatory processes, facilitating the translation of these molecular findings into clinical practice. This review underscores the retina’s potential as a non-invasive window into the molecular pathophysiology of TBI. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Retinal Degeneration and How to Avoid It—2nd Edition)

► Show Figures

Figure 1

19 pages, 4536 KiB

Open AccessReview

Review of Four Refined Clinical Entities in Hereditary Retinal Disorders from Japan

by Yozo Miyake

Int. J. Mol. Sci. 2025, 26(11), 5166; https://doi.org/10.3390/ijms26115166 - 28 May 2025

Viewed by 168

Abstract

In the past, only Oguchi disease was reported as a hereditary retinal disease from Japan. Dr. Chuuta Oguch was a Professor of Nagoya University in Japan. During the past 40 years, four new clinical entities in hereditary retinal disorders have been detected by the Miyake group from Nagoya, Japan. All disorders show essentially normal fundi, and the diagnosis was made mainly by the analysis of an electroretinogram (ERG). Gene mutations are detected in three of them. Bipolar cell (BP) dysfunction syndrome: Congenital stationary night blindness (CSNB) with negative ERG (a-wave is larger than b-wave) was named as the Schubert–Bornschein type in 1952 and considered to be an independent clinical entity. In 1986, Miyake group classified ninety patients with the Schubert–Bornschein type into two types (complete and incomplete type). The complete type of CSNB (CSNB1) showed no rod function, but the incomplete type CSNB (CSNB2) showed remaining rod function in both subjective dark adaptation and rod ERG. In order to investigate the pathogenesis, these two types of CSNB were analyzed by comparing the monkey ERGs using different glutamate analogs to the retina. The ERG analysis demonstrated that CSNB1 has a complete functional defect in the ON type BP, while CSNB2 has incomplete functional defects in the ON and OFF type BP in both rod and cone visual pathways. Evidence of several different genetic heterogeneities was reported in both diseases, indicating CSNB1 and CSNB2 are independent clinical entities. Another entity, showing total complete defect of both ON and OFF BP, was detected in 1974 and was reported by Miyake group in a brother and younger sister, showing severe photophobia, nystagmus, extremely low visual acuity, and disappearance of color vision (total color blindness). This disorder is a congenital stational condition, and subjective visual functions were severely deteriorated from birth but remained unchanged through life. This disease was termed “Total complete bipolar cell dysfunction syndrome (CSNB3)”. The relationship between BP and subjective visual function was unknown. These three kinds of BP diseases can provide information on how BP relates to subjective visual functions. Occult macular dystrophy (OMD): Occult macular dystrophy (OMD) was discovered by Miyake group in 1989. This disease shows an unusual, inherited macular dystrophy characterized by progressive decrease visual acuity due to macular dysfunction, but the fundus and fluorescein angiography are essentially normal. The full-field rod and cone ERG do not show any abnormality, but the focal macular ERG (FERG) or multifocal ERG is abnormal and the only method for diagnosis. Many pedigrees of this disorder suggest autosomal dominant heredity, showing a genetic mutation of RP1L1. This disease was termed “occult macular dystrophy”. “Occult” means “hidden from sight”. Recently, it has been called “Miyake disease”. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Retinal Degeneration and How to Avoid It—2nd Edition)

► Show Figures

Figure 1

19 pages, 572 KiB

Open AccessReview

Short-Chain Fatty Acids and the Gut–Retina Connection: A Systematic Review

by Elena Ciurariu, Andreea-Talida Tirziu, Norberth-Istvan Varga, Bogdan Hirtie, Alexandru Alexandru, Cristiana-Smaranda Ivan and Laura Nicolescu

Int. J. Mol. Sci. 2025, 26(6), 2470; https://doi.org/10.3390/ijms26062470 - 10 Mar 2025

Cited by 1 | Viewed by 1068

Abstract

The interplay between gut microbiota and retinal health, known as the gut-–retina axis, has gained increasing attention in recent years. Short-chain fatty acids (SCFAs), metabolites produced by gut microbiota, have been identified as key mediators of gut–retina communication. This systematic review explores the role of SCFAs in retinal health and their potential impact on the development and progression of retinal diseases, such as diabetic retinopathy (DR), age-related macular degeneration (AMD), and glaucoma. A literature search was conducted across multiple databases, including PubMed, Google Scholar, and Science Direct, to identify studies published between 2014 and December 2024. Studies were included if they investigated the effects of SCFAs on retinal structure, function, or disease pathogenesis in animal models or human subjects. The review included 10 original articles spanning both preclinical and clinical studies. Evidence suggests that SCFAs play a crucial role in maintaining retinal homeostasis through anti-inflammatory and neuroprotective mechanisms. Dysbiosis of the gut microbiota, leading to altered SCFA production, was associated with increased retinal inflammation, oxidative stress, and vascular dysfunction. Furthermore, reduced SCFA levels were linked to the progression of retinal diseases, such as diabetic retinopathy and age-related macular degeneration. Modulation of gut microbiota and SCFA levels through dietary interventions or probiotics may represent a novel therapeutic strategy for preventing or managing retinal diseases. Further research is needed to elucidate the precise molecular mechanisms underlying SCFA-mediated retinal protection and to evaluate the efficacy of targeted therapies in clinical settings. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Retinal Degeneration and How to Avoid It—2nd Edition)

► Show Figures

Figure 1

28 pages, 2189 KiB

Open AccessReview

Understanding the Impact of Polyunsaturated Fatty Acids on Age-Related Macular Degeneration: A Review

by Maëlis Brito, Capucine Sorbier, Nathalie Mignet, Vincent Boudy, Gerrit Borchard and Gaëlle Vacher

Int. J. Mol. Sci. 2024, 25(7), 4099; https://doi.org/10.3390/ijms25074099 - 7 Apr 2024

Cited by 5 | Viewed by 3346

Abstract

Age-related Macular Degeneration (AMD) is a multifactorial ocular pathology that destroys the photoreceptors of the macula. Two forms are distinguished, dry and wet AMD, with different pathophysiological mechanisms. Although treatments were shown to be effective in wet AMD, they remain a heavy burden for patients and caregivers, resulting in a lack of patient compliance. For dry AMD, no real effective treatment is available in Europe. It is, therefore, essential to look for new approaches. Recently, the use of long-chain and very long-chain polyunsaturated fatty acids was identified as an interesting new therapeutic alternative. Indeed, the levels of these fatty acids, core components of photoreceptors, are significantly decreased in AMD patients. To better understand this pathology and to evaluate the efficacy of various molecules, in vitro and in vivo models reproducing the mechanisms of both types of AMD were developed. This article reviews the anatomy and the physiological aging of the retina and summarizes the clinical aspects, pathophysiological mechanisms of AMD and potential treatment strategies. In vitro and in vivo models of AMD are also presented. Finally, this manuscript focuses on the application of omega-3 fatty acids for the prevention and treatment of both types of AMD. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Retinal Degeneration and How to Avoid It—2nd Edition)

► Show Figures

Figure 1

19 pages, 1854 KiB

Open AccessReview

The Role of Galectin-3 in Retinal Degeneration and Other Ocular Diseases: A Potential Novel Biomarker and Therapeutic Target

by Ziyi Zhou, Zhaochen Feng, Xiaojia Sun, Yusheng Wang and Guorui Dou

Int. J. Mol. Sci. 2023, 24(21), 15516; https://doi.org/10.3390/ijms242115516 - 24 Oct 2023

Cited by 3 | Viewed by 2680

Abstract

Galectin-3 is the most studied member of the Galectin family, with a large range of mediation in biological activities such as cell growth, proliferation, apoptosis, differentiation, cell adhesion, and tissue repair, as well as in pathological processes such as inflammation, tissue fibrosis, and angiogenesis. As is known to all, inflammation, aberrant cell apoptosis, and neovascularization are the main pathophysiological processes in retinal degeneration and many ocular diseases. Therefore, the review aims to conclude the role of Gal3 in the retinal degeneration of various diseases as well as the occurrence and development of the diseases and discuss its molecular mechanisms according to research in systemic diseases. At the same time, we summarized the predictive role of Gal3 as a biomarker and the clinical application of its inhibitors to discuss the possibility of Gal3 as a novel target for the treatment of ocular diseases. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Retinal Degeneration and How to Avoid It—2nd Edition)

► Show Figures

Figure 1

17 pages, 1069 KiB

Open AccessReview

Neurovascular Cell Death and Therapeutic Strategies for Diabetic Retinopathy

by Toshiyuki Oshitari

Int. J. Mol. Sci. 2023, 24(16), 12919; https://doi.org/10.3390/ijms241612919 - 18 Aug 2023

Cited by 10 | Viewed by 3064

Abstract

Diabetic retinopathy (DR) is a major complication of diabetes and a leading cause of blindness worldwide. DR was recently defined as a neurovascular disease associated with tissue-specific neurovascular impairment of the retina in patients with diabetes. Neurovascular cell death is the main cause of neurovascular impairment in DR. Thus, neurovascular cell protection is a potential therapy for preventing the progression of DR. Growing evidence indicates that a variety of cell death pathways, such as apoptosis, necroptosis, ferroptosis, and pyroptosis, are associated with neurovascular cell death in DR. These forms of regulated cell death may serve as therapeutic targets for ameliorating the pathogenesis of DR. This review focuses on these cell death mechanisms and describes potential therapies for the treatment of DR that protect against neurovascular cell death. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Retinal Degeneration and How to Avoid It—2nd Edition)

► Show Figures

Journal Menu

Journal Browser

Molecular Mechanisms of Retinal Degeneration and How to Avoid It—2nd Edition

Share This Special Issue

Special Issue Editors

Special Issue Information

Keywords

Benefits of Publishing in a Special Issue

Published Papers (8 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI