International Journal of Molecular Sciences

Editorial

Jump to: Research, Review, Other

5 pages, 152 KB

Open AccessEditorial

Special Issue “Advances in Retinal Diseases: 2nd Edition”

by Minzhong Yu

Int. J. Mol. Sci. 2026, 27(5), 2187; https://doi.org/10.3390/ijms27052187 - 26 Feb 2026

Viewed by 412

Abstract

Retinal diseases continue to command the attention of clinicians and scientists alike because they compress complex biology into the span of a single, fragile tissue and translate molecular perturbations into life-altering vision loss [...] Full article

(This article belongs to the Special Issue Advances in Retinal Diseases: 2nd Edition)

Research

Jump to: Editorial, Review, Other

24 pages, 6346 KB

Open AccessArticle

Nonsense Mutation in USH2A Exon-13 Activates the Innate Immune Response in Müller Glial Cells

by Rossella Valenzano, Xuefei Lu, Andrew McDonald, Ioannis Moustakas, Roberta Menafra, Aat A. Mulder, Roman I. Koning, Susan L. Kloet, Jun Yang, Hailiang Mei and Jan Wijnholds

Int. J. Mol. Sci. 2026, 27(4), 1636; https://doi.org/10.3390/ijms27041636 - 7 Feb 2026

Viewed by 735

Abstract

Pathological USH2A mutations cause Usher syndrome type II, characterized by progressive retinitis pigmentosa and hearing and balance impairment. This study aims to investigate the cellular mechanisms underlying USH2A-related retinal degeneration using human induced pluripotent stem cell (hiPSC)-derived retinal organoids. The introduction of [...] Read more.

Pathological USH2A mutations cause Usher syndrome type II, characterized by progressive retinitis pigmentosa and hearing and balance impairment. This study aims to investigate the cellular mechanisms underlying USH2A-related retinal degeneration using human induced pluripotent stem cell (hiPSC)-derived retinal organoids. The introduction of a homozygous nonsense mutation in the USH2A hotspot exon-13 resulted in normal photoreceptor development but loss of ciliary localization of usherin long form B and its interacting proteins, ADGRV1 and whirlin. Notably, single-cell RNA sequencing revealed unexpected significant transcriptional changes in Müller glial cells (MGCs), suggestive of disruptions in the translation, innate immune response, and endolysosomal system. These findings suggest that, while photoreceptor cells are mildly affected by the exon-13 USH2A mutation, MGCs exhibit major transcriptional changes, potentially contributing to the disease progression and therefore shedding light on potential alternative therapeutic targets. Full article

(This article belongs to the Special Issue Advances in Retinal Diseases: 2nd Edition)

► Show Figures

Figure 1

18 pages, 15410 KB

Open AccessArticle

Patterns of Inflammation in Experimental Autoimmune Uveitis and Their Correlation to Optical Coherence Tomography Findings in Human Uveitis

by Benedikt Schworm, Tarek Ghannoum, Stephan Thurau and Gerhild Wildner

Int. J. Mol. Sci. 2026, 27(4), 1618; https://doi.org/10.3390/ijms27041618 - 7 Feb 2026

Viewed by 633

Abstract

Experimental autoimmune uveitis (EAU) in rats is a pivotal model for understanding the immunological mechanisms of human uveitis and developing therapies. In humans, optical coherence tomography (OCT) allows for the in vivo detection of characteristic findings in active uveitis, as well as sequelae [...] Read more.

Experimental autoimmune uveitis (EAU) in rats is a pivotal model for understanding the immunological mechanisms of human uveitis and developing therapies. In humans, optical coherence tomography (OCT) allows for the in vivo detection of characteristic findings in active uveitis, as well as sequelae of inflammation. The objective of this study was to correlate OCT findings in patients with uveitis with retinal histologies from two rat models of EAU caused by T cells with different autoantigen specificities and well-known underlying immunological pathomechanisms. Patients with various noninfectious uveitis subtypes underwent imaging using an ultra-widefield swept source or conventional OCT. Histological cryosections from rat eyes with experimental autoimmune uveitis were stained for T cell and/or macrophage markers. Typical human OCT findings were reproduced in the experimental animal model. Hyperreflective signals observed on OCT corresponded to lymphocyte infiltration in histological sections. This infiltration was typically found as vasculitis in the perivascular regions and snowballs in the posterior hyaloid. There was lymphocyte and macrophage infiltration of the retina through the retinal vessels and the retinal pigment epithelium. Comparing in vivo OCT imaging of human uveitis with corresponding histologies from rat models improves our understanding of the type of inflammation, extent of tissue destruction, and immunopathogenesis. Full article

(This article belongs to the Special Issue Advances in Retinal Diseases: 2nd Edition)

► Show Figures

Figure 1

18 pages, 1711 KB

Open AccessArticle

Functional In Vitro Assessment of rAAV-Delivered Retinol Dehydrogenase 12 (RDH12) Activity

by Polina Pavlova, Marina Averina, Dzerassa Gurtsieva, Alima Galieva, Roman A. Ivanov, Alexander Karabelsky and Ekaterina Minskaia

Int. J. Mol. Sci. 2026, 27(3), 1366; https://doi.org/10.3390/ijms27031366 - 29 Jan 2026

Viewed by 920

Abstract

Gene replacement therapy can be used for the treatment of hereditary retinopathies, such as retinol dehydrogenase 12 (RDH12)-associated Leber congenital amaurosis 13 (LCA13); however, the lack of animal models accurately mimicking the human disease phenotype requires the initial in vitro confirmation of therapy [...] Read more.

Gene replacement therapy can be used for the treatment of hereditary retinopathies, such as retinol dehydrogenase 12 (RDH12)-associated Leber congenital amaurosis 13 (LCA13); however, the lack of animal models accurately mimicking the human disease phenotype requires the initial in vitro confirmation of therapy efficacy. Two synthetic serotypes (2.7m8 and PHP.S) of adeno-associated virus (AAV) were tested against the natural serotypes (5 and 9) with the aim of increasing the transduction efficiency and delivery of the green fluorescent protein (GFP) in HEK293 and ARPE-19 cells. The three most efficient serotypes were then used for the delivery of RDH12, followed by the assessment of its functional activity in the transduced cells. In the in vitro test system, a cassette encoding GFP and the wild-type (wt) RDH12 was delivered into ARPE-19 and HEK293 cells by rAAV 5, PHP.S, and 7m8 at 30K and 60K VG/cell. RDH12 mutants pThr155Ile (RDH12mut) and Met1* (RDH12sc) were used to mimic the RDH12-associated pathology. Transduction efficiency and protein expression were assessed by flow cytometry, fluorescence microscopy, and Western blotting. Percentages of AAV7m8-transduced GFP+ cells 1.5- and 6.4-times higher were observed as compared to AAV5 and AAV.PHP.S, respectively. 4-hydroxynonenal (4-HNE), more toxic to the cells with dysfunctional RDH12, was used on cells expressing the three RDH12wt versions. Following treatment with 100 μM 4-HNE, 2.6 (AAV5) and 8.8 (AAV7m8) times more cells co-expressing RDH12wt and GFP were alive as compared to the cells expressing only GFP. The number of live RDH12wt-expressing cells was also 32 and 9.6 times higher than that of RDH12sc-expressing cells and the negative control (NC), respectively. The developed approach enables the functional assessment of RDH12 replacement therapy only in rAAV-transduced cells and demonstrates that rAAV7m8 is the most efficient serotype for this purpose. Full article

(This article belongs to the Special Issue Advances in Retinal Diseases: 2nd Edition)

► Show Figures

Graphical abstract

19 pages, 3471 KB

Open AccessArticle

The Specific Pathogenicity Pattern of the Different CRB1 Isoforms Conditions Clinical Severity in Inherited Retinal Dystrophies

by Laura Siles, Sheila Ruiz-Nogales, Pilar Méndez-Vendrell, Anniken Burés-Jelstrup, Rafael Navarro and Esther Pomares

Int. J. Mol. Sci. 2025, 26(23), 11551; https://doi.org/10.3390/ijms262311551 - 28 Nov 2025

Cited by 1 | Viewed by 818

Abstract

Pathogenic variants in Crumbs homolog 1 (CRB1) cause a wide range of severe ocular diseases, most commonly Leber congenital amaurosis and other forms of adult-onset macular dystrophy that lead to vision loss. Despite this broad clinical spectrum, the expression and function [...] Read more.

Pathogenic variants in Crumbs homolog 1 (CRB1) cause a wide range of severe ocular diseases, most commonly Leber congenital amaurosis and other forms of adult-onset macular dystrophy that lead to vision loss. Despite this broad clinical spectrum, the expression and function of CRB1 in retinal cells remains underexplored. In this study, we show a comprehensive characterization of CRB1 isoforms in several human retinal models like retinal organoids. Although CRB1 is predominantly expressed in photoreceptors and Müller glial cells, we also detected its expression in the human retinal pigment epithelium (RPE). Moreover, we observed defined expression patterns of CRB1 isoforms depending on the maturation stage of retinal cells, suggesting a role for this protein in development and differentiation. In this context, the less abundant and less studied isoform CRB1-C was the most highly expressed in early undifferentiated stages of photoreceptors and in RPE. Additionally, clinical and genetic evaluation of a cohort of 25 probands carrying pathogenic CRB1 variants allowed us to propose a genotype–phenotype correlation between isoforms involvement and disease severity, and to the identification of four novel pathogenic variants: p.Met70ArgfsTer17, p.Cys136Phe, p.Cys248Ser and p.Gln1094Ter. Collectively, our data elucidate previously undescribed expression patterns of CRB1 isoforms during retinal cell differentiation and highlight key aspects of CRB1-associated inherited retinal dystrophies. Full article

(This article belongs to the Special Issue Advances in Retinal Diseases: 2nd Edition)

► Show Figures

Figure 1

24 pages, 6246 KB

Open AccessArticle

Anti-Herpes Simplex Virus Type 1 Activity of Rosa damascena Mill Essential Oil and Floral Water in Retinal Infection In Vitro and In Silico

by Neli Vilhelmova-Ilieva, Rayna Nenova, Kalin Kalinov, Ana Dobreva, Dimitar Peshev and Ivan Iliev

Int. J. Mol. Sci. 2025, 26(15), 7521; https://doi.org/10.3390/ijms26157521 - 4 Aug 2025

Cited by 1 | Viewed by 2469

Abstract

Recently, essential rose oils and rose products have gained increasing importance in both the cosmetic and food industries, as well as in the composition of medicinal products. We investigated the in vitro antiviral activity of essential oil and floral water from Rosa damascena [...] Read more.

Recently, essential rose oils and rose products have gained increasing importance in both the cosmetic and food industries, as well as in the composition of medicinal products. We investigated the in vitro antiviral activity of essential oil and floral water from Rosa damascena Mill against herpes simplex virus type 1 (HSV-1) infection in rabbit retinal cells (RRCs). The composition of the main chemical components in the rose essential oil was determined by means of gas chromatographic analysis. The effect on the viral replication cycle was determined using the cytopathic effect (CPE) inhibition assay. The virucidal activity, the effect on the adsorption stage of the virus to the host cell, and the protective effect on healthy cells were evaluated using the endpoint dilution method. The effects were determined as deviation in the viral titer, Δlg, for the treated cells from the one for the untreated viral control. The identified main active components of rose oil are geraniol (28.73%), citronellol (21.50%), nonadecane (13.13%), nerol (5.51%), heneicosane (4.87%), nonadecene (3.93), heptadecane (2.29), farnesol (2.11%), tricosane (1.29%), eicosane (1.01%), and eugenol (0.85%). The results demonstrated that both rose products do not have a significant effect on the virus replication but directly affect the viral particles and reduce the viral titer by Δlg = 3.25 for floral water and by Δlg = 3.0 for essential oil. Significant inhibition of the viral adsorption stage was also observed, leading to a decrease in the viral titers by Δlg = 2.25 for floral water and by Δlg = 2.0 for essential oil. When pretreating healthy cells with rose products, both samples significantly protected them from subsequent infection with HSV-1. This protective effect was more pronounced for the oil (Δlg = 2.5) compared to the one for the floral water (Δlg = 2.0). We used the in silico molecular docking method to gain insight into the mechanism of hindrance of viral adsorption by the main rose oil compounds (geraniol, citronellol, nerol). These components targeted the HSV-1 gD interaction surface with nectin-1 and HVEM (Herpesvirus Entry Mediator) host cell receptors, at N-, C-ends, and N-end, respectively. These findings could provide a structural framework for further development of anti-HSV-1 therapeutics. Full article

(This article belongs to the Special Issue Advances in Retinal Diseases: 2nd Edition)

► Show Figures

Figure 1

19 pages, 4864 KB

Open AccessArticle

Müller Glia Co-Regulate Barrier Permeability with Endothelial Cells in an Vitro Model of Hyperglycemia

by Juan S. Peña, François Berthiaume and Maribel Vazquez

Int. J. Mol. Sci. 2024, 25(22), 12271; https://doi.org/10.3390/ijms252212271 - 15 Nov 2024

Cited by 8 | Viewed by 5768

Abstract

Diabetic retinopathy is a complex, microvascular disease that impacts millions of working adults each year. High blood glucose levels from Diabetes Mellitus lead to the accumulation of advanced glycation end-products (AGEs), which promote inflammation and the breakdown of the inner blood retinal barrier [...] Read more.

Diabetic retinopathy is a complex, microvascular disease that impacts millions of working adults each year. High blood glucose levels from Diabetes Mellitus lead to the accumulation of advanced glycation end-products (AGEs), which promote inflammation and the breakdown of the inner blood retinal barrier (iBRB), resulting in vision loss. This study used an in vitro model of hyperglycemia to examine how endothelial cells (ECs) and Müller glia (MG) collectively regulate molecular transport. Changes in cell morphology, the expression of junctional proteins, and the reactive oxygen species (ROS) of ECs and MG were examined when exposed to a hyperglycemic medium containing AGEs. Trans-endothelial resistance (TEER) assays were used to measure the changes in cell barrier resistance in response to hyperglycemic and inflammatory conditions, with and without an anti-VEGF compound. Both of the cell types responded to hyperglycemic conditions with significant changes in the cell area and morphology, the ROS, and the expression of the junctional proteins ZO-1, CX-43, and CD40, as well as the receptor for AGEs. The resistivities of the individual and dual ECs and MG barriers decreased within the hyperglycemia model but were restored to that of basal, normoglycemic levels when treated with anti-VEGF. This study illustrated significant phenotypic responses to an in vitro model of hyperglycemia, as well as significant changes in the expression of the key proteins used for cell–cell communication. The results highlight important, synergistic relationships between the ECs and MG and how they contribute to changes in barrier function in combination with conventional treatments. Full article

(This article belongs to the Special Issue Advances in Retinal Diseases: 2nd Edition)

► Show Figures

Figure 1

18 pages, 1541 KB

Open AccessArticle

Phenotypic and Genetic Spectrum in 309 Consecutive Pediatric Patients with Inherited Retinal Disease

by Claudia S. Priglinger, Maximilian J. Gerhardt, Siegfried G. Priglinger, Markus Schaumberger, Teresa M. Neuhann, Hanno J. Bolz, Yasmin Mehraein and Guenther Rudolph

Int. J. Mol. Sci. 2024, 25(22), 12259; https://doi.org/10.3390/ijms252212259 - 14 Nov 2024

Cited by 5 | Viewed by 2882

Abstract

Inherited retinal dystrophies (IRDs) are a common cause of blindness or severe visual impairment in children and may occur with or without systemic associations. The aim of the present study is to describe the phenotypic and genotypic spectrum of IRDs in a pediatric [...] Read more.

Inherited retinal dystrophies (IRDs) are a common cause of blindness or severe visual impairment in children and may occur with or without systemic associations. The aim of the present study is to describe the phenotypic and genotypic spectrum of IRDs in a pediatric patient cohort in Retrospective single-center cross-sectional analysis. Presenting symptoms, clinical phenotype, and molecular genetic diagnosis were assessed in 309 pediatric patients with suspected IRD. Patients were grouped by age at genetic diagnosis (preschool: 0–6 years, n = 127; schoolchildren: 7–17 years, n = 182). Preschool children most frequently presented with nystagmus (34.5% isolated, 16.4% syndromic), no visual interest (20.9%; 14.5%), or nyctalopia (22.4%; 3.6%; p < 0.05); schoolchildren most frequently presented with declining visual acuity (31% isolated, 21.1% syndromic), nyctalopia (10.6%; 13.5%), or high myopia (5.3%; 13.2%). Pathogenic variants were identified in 96 different genes (n = 69 preschool, n = 73 schoolchildren). In the preschool group, 57.4% had isolated and 42.6% had syndromic IRDs, compared to 70.9% and 29.1% in schoolchildren. In the preschool group, 32.4% of the isolated IRDs were related to forms of Leber’s congenital amaurosis (most frequent were RPE65 (11%) and CEP290 (8.2%)), 31.5% were related to stationary IRDs, 15.1% were related to macular dystrophies (ABCA4, BEST1, PRPH2, PROM1), and 8.2% to rod–cone dystrophies (RPGR, RPB3, RP2, PDE6A). All rod–cone dystrophies (RCDs) were subjectively asymptomatic at the time of genetic diagnosis. At schoolage, 41% were attributed to cone-dominated disease (34% ABCA4), 10.3% to BEST1, and 10.3% to RCDs (RP2, PRPF3, RPGR; IMPG2, PDE6B, CNGA1, MFRP, RP1). Ciliopathies were the most common syndromic IRDs (preschool 37%; schoolchildren 45.1%), with variants in USH2A, CEP290 (5.6% each), CDH23, BBS1, and BBS10 (3.7% each) being the most frequent in preschoolers, and USH2A (11.7%), BBS10 (7.8%), CEP290, CDHR23, CLRN1, and ICQB1 (3.9% each) being the most frequent in syndromic schoolkids. Vitreoretinal syndromic IRDs accounted for 29.6% (preschool: COL2A1, COL11A1, NDP (5.6% each)) and 23.5% (schoolage: COL2A1, KIF11 (9.8% each)), metabolic IRDs for 9.4% (OAT, HADHA, MMACHD, PMM2) and 3.9% (OAT, HADHA), mitochondriopathies for 3.7% and 7.8%, and syndromic albinism accounted for 5.6% and 3.9%, respectively. In conclusion we show here that the genotypic spectrum of IRDs and its quantitative distribution not only differs between children and adults but also between children of different age groups, with an almost equal proportion of syndromic and non-syndromic IRDs in early childhood. Ophthalmic screening visits at the preschool and school ages may aid even presymptomatic diagnosis and treatment of potential sight and life-threatening systemic sequelae. Full article

(This article belongs to the Special Issue Advances in Retinal Diseases: 2nd Edition)

► Show Figures

Figure 1

17 pages, 2360 KB

Open AccessArticle

AAV-NDI1 Therapy Provides Significant Benefit to Murine and Cellular Models of Glaucoma

by Sophia Millington-Ward, Arpad Palfi, Ciara Shortall, Laura K. Finnegan, Ethan Bargroff, Iris J. M. Post, John Maguire, Mustapha Irnaten, Colm O′Brien, Paul F. Kenna, Naomi Chadderton and G. Jane Farrar

Int. J. Mol. Sci. 2024, 25(16), 8876; https://doi.org/10.3390/ijms25168876 - 15 Aug 2024

Cited by 6 | Viewed by 7003

Abstract

Glaucoma, a leading cause of blindness, is a multifactorial condition that leads to progressive loss of retinal ganglion cells (RGCs) and vision. Therapeutic interventions based on reducing ocular hypertension are not always successful. Emerging features of glaucoma include mitochondrial dysfunction and oxidative stress. [...] Read more.

Glaucoma, a leading cause of blindness, is a multifactorial condition that leads to progressive loss of retinal ganglion cells (RGCs) and vision. Therapeutic interventions based on reducing ocular hypertension are not always successful. Emerging features of glaucoma include mitochondrial dysfunction and oxidative stress. In the current study, NDI1-based gene therapy, which improves mitochondrial function and reduces reactive oxygen species, was delivered intraocularly via an adeno-associated viral vector (AAV). This AAV-NDI1 therapy protected RGCs from cell death in treated (1552.4 ± 994.0 RGCs/mm²) versus control eyes (1184.4 ± 978.4 RGCs/mm², p < 0.05) in aged DBA/2J mice, a murine model of glaucoma. The photonegative responses (PhNRs) of RGCs were also improved in treated (6.4 ± 3.3 µV) versus control eyes (5.0 ± 3.1 µV, p < 0.05) in these mice. AAV-NDI1 also provided benefits in glaucomatous human lamina cribrosa (LC) cells by significantly increasing basal and maximal oxygen consumption rates and ATP production in these cells. Similarly, NDI1 therapy significantly protected H₂O₂-insulted primary porcine LC cells from oxidative stress. This study highlights the potential utility of NDI1 therapies and the benefits of improving mitochondrial function in the treatment of glaucoma. Full article

(This article belongs to the Special Issue Advances in Retinal Diseases: 2nd Edition)

► Show Figures

Graphical abstract

16 pages, 288 KB

Open AccessArticle

Limited Added Diagnostic Value of Whole Genome Sequencing in Genetic Testing of Inherited Retinal Diseases in a Swiss Patient Cohort

by Jordi Maggi, Samuel Koller, Silke Feil, Ruxandra Bachmann-Gagescu, Christina Gerth-Kahlert and Wolfgang Berger

Int. J. Mol. Sci. 2024, 25(12), 6540; https://doi.org/10.3390/ijms25126540 - 13 Jun 2024

Cited by 11 | Viewed by 3221

Abstract

The purpose of this study was to assess the added diagnostic value of whole genome sequencing (WGS) for patients with inherited retinal diseases (IRDs) who remained undiagnosed after whole exome sequencing (WES). WGS was performed for index patients in 66 families. The datasets [...] Read more.

The purpose of this study was to assess the added diagnostic value of whole genome sequencing (WGS) for patients with inherited retinal diseases (IRDs) who remained undiagnosed after whole exome sequencing (WES). WGS was performed for index patients in 66 families. The datasets were analyzed according to GATK’s guidelines. Additionally, DeepVariant was complemented by GATK’s workflow, and a novel structural variant pipeline was developed. Overall, a molecular diagnosis was established in 19/66 (28.8%) index patients. Pathogenic deletions and one deep-intronic variant contributed to the diagnostic yield in 4/19 and 1/19 index patients, respectively. The remaining diagnoses (14/19) were attributed to exonic variants that were missed during WES analysis due to bioinformatic limitations, newly described loci, or unclear pathogenicity. The added diagnostic value of WGS equals 5/66 (9.6%) for our cohort, which is comparable to previous studies. This figure would decrease further to 1/66 (1.5%) with a standardized and reliable copy number variant workflow during WES analysis. Given the higher costs and limited added value, the implementation of WGS as a first-tier assay for inherited eye disorders in a diagnostic laboratory remains untimely. Instead, progress in bioinformatic tools and communication between diagnostic and clinical teams have the potential to ameliorate diagnostic yields. Full article

(This article belongs to the Special Issue Advances in Retinal Diseases: 2nd Edition)

Review

Jump to: Editorial, Research, Other

37 pages, 7101 KB

Open AccessReview

Integrative Landscape of Dry AMD Pathogenesis, Models, and Emerging Therapeutic Strategies

by Shiva Kumar Bhandari, Sooyeun Lee and Hye Jin Kim

Int. J. Mol. Sci. 2026, 27(1), 202; https://doi.org/10.3390/ijms27010202 - 24 Dec 2025

Cited by 2 | Viewed by 2642

Abstract

Dry age-related macular degeneration (AMD) is the leading cause of central vision loss among the elderly, yet no curative treatment exists. While exudative AMD can be managed with anti-vascular endothelial growth factor (VEGF) therapy, dry AMD—accounting for more than 85% of cases—progresses insidiously [...] Read more.

Dry age-related macular degeneration (AMD) is the leading cause of central vision loss among the elderly, yet no curative treatment exists. While exudative AMD can be managed with anti-vascular endothelial growth factor (VEGF) therapy, dry AMD—accounting for more than 85% of cases—progresses insidiously from drusen accumulation to geographic atrophy (GA). Although the recent U.S. Food and Drug Administration (FDA) approvals of pegcetacoplan and avacincaptad pegol represent major milestones, their therapeutic effects remain modest. This review provides an integrated overview of the molecular and cellular mechanisms underlying dry AMD, highlighting key pathogenic pathways involving oxidative stress, lipid dysregulation, complement activation, mitochondrial impairment, and RPE-specific bisretinoid lipofuscin accumulation. We further summarize mechanistic mouse models that replicate these pathological processes and discuss how each model contributes to understanding the disease. Finally, we review current and emerging therapeutic strategies—including complement inhibitors, visual cycle modulators, and mitochondrial-protective approaches—and outline future directions for translational research. Collectively, this review synthesizes mechanistic insights, disease models, and therapeutic innovation to support the development of targeted and stage-specific interventions for dry AMD. Full article

(This article belongs to the Special Issue Advances in Retinal Diseases: 2nd Edition)

► Show Figures

Figure 1

36 pages, 10348 KB

Open AccessReview

The Role of Visual Electrophysiology in Systemic Hereditary Syndromes

by Minzhong Yu, Emile R. Vieta-Ferrer, Anas Bakdalieh and Travis Tsai

Int. J. Mol. Sci. 2025, 26(3), 957; https://doi.org/10.3390/ijms26030957 - 23 Jan 2025

Cited by 3 | Viewed by 4031

Abstract

Visual electrophysiology is a valuable tool for evaluating the visual system in various systemic syndromes. This review highlights its clinical application in a selection of syndromes associated with hearing loss, mitochondrial dysfunction, obesity, and other multisystem disorders. Techniques such as full-field electroretinography (ffERG), [...] Read more.

Visual electrophysiology is a valuable tool for evaluating the visual system in various systemic syndromes. This review highlights its clinical application in a selection of syndromes associated with hearing loss, mitochondrial dysfunction, obesity, and other multisystem disorders. Techniques such as full-field electroretinography (ffERG), multifocal electroretinography (mfERG), pattern electroretinography (PERG), visual evoked potentials (VEP), and electrooculography (EOG) offer insights into retinal and optic nerve function, often detecting abnormalities before clinical symptoms manifest. In hearing loss syndromes like Refsum disease, Usher syndrome (USH), and Wolfram syndrome (WS), electrophysiology facilitates the detection of early retinal changes that precede the onset of visual symptoms. For mitochondrial disorders such as maternally-inherited diabetes and deafness (MIDD), Kearns–Sayre syndrome (KSS), and neuropathy, ataxia, and retinitis pigmentosa (NARP) syndrome, these tests can be useful in characterizing retinal degeneration and optic neuropathy. In obesity syndromes, including Bardet-Biedl syndrome (BBS), Alström syndrome, and Cohen syndrome, progressive retinal degeneration is a hallmark feature. Electrophysiological techniques aid in pinpointing retinal dysfunction and tracking disease progression. Other syndromes, such as Alagille syndrome (AGS), abetalipoproteinemia (ABL), Cockayne syndrome (CS), Joubert syndrome (JS), mucopolysaccharidosis (MPS), Neuronal ceroid lipofuscinoses (NCLs), and Senior–Løken syndrome (SLS), exhibit significant ocular involvement that can be evaluated using these methods. This review underscores the role of visual electrophysiology in diagnosing and monitoring visual system abnormalities across a range of syndromes, potentially offering valuable insights for early diagnosis, monitoring of progression, and management. Full article

(This article belongs to the Special Issue Advances in Retinal Diseases: 2nd Edition)

► Show Figures

Figure 1

20 pages, 2473 KB

Open AccessReview

Natural Products in the Treatment of Retinopathy of Prematurity: Exploring Therapeutic Potentials

by Jong-Ik Heo and Juhee Ryu

Int. J. Mol. Sci. 2024, 25(15), 8461; https://doi.org/10.3390/ijms25158461 - 2 Aug 2024

Cited by 1 | Viewed by 2807

Abstract

Retinopathy of prematurity (ROP) is a vascular disorder affecting the retinas of preterm infants. This condition arises when preterm infants in incubators are exposed to high oxygen levels, leading to oxidative stress, inflammatory responses, and a downregulation of vascular endothelial growth factors, which [...] Read more.

Retinopathy of prematurity (ROP) is a vascular disorder affecting the retinas of preterm infants. This condition arises when preterm infants in incubators are exposed to high oxygen levels, leading to oxidative stress, inflammatory responses, and a downregulation of vascular endothelial growth factors, which causes the loss of retinal microvascular capillaries. Upon returning to room air, the upregulation of vascular growth factors results in abnormal vascular growth of retinal endothelial cells. Without appropriate intervention, ROP can progress to blindness. The prevalence of ROP has risen, making it a significant cause of childhood blindness. Current treatments, such as laser therapy and various pharmacologic approaches, are limited by their potential for severe adverse effects. Therefore, a deeper understanding of ROP’s pathophysiology and the development of innovative treatments are imperative. Natural products from plants, fungi, bacteria, and marine organisms have shown promise in treating various diseases and have gained attention in ROP research due to their minimal side effects and wide-ranging beneficial properties. This review discusses the roles and mechanisms of natural products that hold potential as therapeutic agents in ROP management. Full article

(This article belongs to the Special Issue Advances in Retinal Diseases: 2nd Edition)

► Show Figures

Figure 1

18 pages, 1121 KB

Open AccessReview

Metabolic Regulation of Endothelial Cells: A New Era for Treating Wet Age-Related Macular Degeneration

by Xirui Chen, Yang Xu, Yahan Ju and Ping Gu

Int. J. Mol. Sci. 2024, 25(11), 5926; https://doi.org/10.3390/ijms25115926 - 29 May 2024

Cited by 4 | Viewed by 4297

Abstract

Wet age-related macular degeneration (wet AMD) is a primary contributor to visual impairment and severe vision loss globally, but the prevailing treatments are often unsatisfactory. The development of conventional treatment strategies has largely been based on the understanding that the angiogenic switch of [...] Read more.

Wet age-related macular degeneration (wet AMD) is a primary contributor to visual impairment and severe vision loss globally, but the prevailing treatments are often unsatisfactory. The development of conventional treatment strategies has largely been based on the understanding that the angiogenic switch of endothelial cells (ECs) is mainly dictated by angiogenic growth factors. Even though treatments targeting vascular endothelial growth factor (VEGF), like ranibizumab, are widely administered, more than half of patients still exhibit inadequate or null responses, suggesting the involvement of other pathogenic mechanisms. With advances in research in recent years, it has become well recognized that EC metabolic regulation plays an active rather than merely passive responsive role in angiogenesis. Disturbances of these metabolic pathways may lead to excessive neovascularization in angiogenic diseases such as wet AMD, therefore targeted modulation of EC metabolism represents a promising therapeutic strategy for wet AMD. In this review, we comprehensively discuss the potential applications of EC metabolic regulation in wet AMD treatment from multiple perspectives, including the involvement of ECs in wet AMD pathogenesis, the major endothelial metabolic pathways, and novel therapeutic approaches targeting metabolism for wet AMD. Full article

(This article belongs to the Special Issue Advances in Retinal Diseases: 2nd Edition)

► Show Figures

Figure 1

Other

Jump to: Editorial, Research, Review

7 pages, 1607 KB

Open AccessCase Report

Floaters as the First Manifestation of Chronic Myeloid Leukemia: A Case Report

by Siyun Lee and Joonhyung Kim

Int. J. Mol. Sci. 2025, 26(18), 8841; https://doi.org/10.3390/ijms26188841 - 11 Sep 2025

Viewed by 1368

Abstract

Chronic myeloid leukemia (CML) is a clonal myeloproliferative neoplasm arising in hematopoietic stem cells. It may initially present with ocular symptoms, as illustrated by the case of a previously healthy 25-year-old woman who presented with a five-day history of floaters in her left [...] Read more.

Chronic myeloid leukemia (CML) is a clonal myeloproliferative neoplasm arising in hematopoietic stem cells. It may initially present with ocular symptoms, as illustrated by the case of a previously healthy 25-year-old woman who presented with a five-day history of floaters in her left eye. Fundus examination revealed bilateral retinal hemorrhages, Roth spots, increased vascular tortuosity, a left preretinal hemorrhage, and a left vitreous hemorrhage. Retinopathy secondary to a hematologic disorder was considered; the patient was promptly referred to hematology–oncology. Laboratory evaluation demonstrated leukocytosis with anemia, peripheral smear showed 1% myeloblasts, 40% myelocytes, and basophilia. Cytogenetic analysis confirmed t(9;22)(q34;q11.2), and quantitative polymerase chain reaction (PCR) detected a BCR::ABL1 (b3a2) transcript. A diagnosis of bilateral leukemic retinopathy was established, and the patient promptly started appropriate therapy for CML. This case underscores the importance of recognizing ocular findings—such as Roth spots, intraocular hemorrhages, and increased vascular tortuosity—as potential indicators of systemic malignancy and ensuring early referral and management. Early ophthalmic recognition of such findings can be vision- and life-saving. Full article

(This article belongs to the Special Issue Advances in Retinal Diseases: 2nd Edition)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Advances in Retinal Diseases: 2nd Edition

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Benefits of Publishing in a Special Issue

Related Special Issue

Published Papers (15 papers)

Editorial

Research

Review

Other

Further Information

Guidelines

MDPI Initiatives

Follow MDPI