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Molecular Mechanisms and Treatment of Retinal Diseases
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Molecular Mechanisms and Treatment of Retinal Diseases

A Special Issue of International Journal of Molecular Sciences (ISSN 1422-0067) belonging to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (30 November 2025) | Viewed by 21965

Editors

Dr. Deokho Lee

E-Mail Website
Guest Editor
1. The Korean Institute of Nutrition, Hallym University, Chuncheon, Republic of Korea
2. Laboratory of Photobiology, Keio University School of Medicine, Tokyo, Japan
Interests: retinal degeneration; oxidative stress; glaucoma; choroidal neovascularization; vitamin nutrition; retinal diseases
Special Issues, Collections and Topics in MDPI journals
Dr. Livio Vitiello

E-Mail Website
Guest Editor
Eye Unit, Department of Medicine, Surgery and Dentistry, "Scuola Medica Salernitana", University of Salerno, Baronissi, Salerno, Italy
Interests: ophthalmology; ocular ultrasound; medical retina; retinal diseases; glaucoma; optic nerve
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The retina in the eye is essential for vision and is highly vulnerable to a range of pathological insults. Retinal degeneration due to aging, inflammation, and vascular damage remains a major cause of irreversible vision loss worldwide. In recent years, significant attention has been directed toward the role of metabolic regulation in maintaining retinal health, particularly in the context of high myopia, age-related macular degeneration, and glaucoma. Clinical and experimental studies suggest that targeted nutrients may exert protective effects by reducing oxidative stress, modulating inflammation, and preserving retinal integrity. Furthermore, innovative therapies such as cell-based treatments and advanced drug delivery systems, including eye drops capable of crossing ocular barriers, have emerged as promising strategies to restore or preserve vision. Light therapy has also gained interest as a non-invasive modality to modulate retinal physiology and potentially slow down degenerative progression.

This Special Issue will focus on recent advances across multiple fronts—including nutritional interventions, optometric management, regenerative therapies, drug delivery innovations, and digital health applications to address retinal degeneration, ischemia, and inflammatory retinal disorders in various eye diseases. By bringing together cutting-edge research and clinical insights, this collection can inspire new therapeutic strategies that can protect vision and enhance quality of life worldwide.

Dr. Deokho Lee
Dr. Livio Vitiello
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 250 words) can be sent to the Editorial Office for assessment.

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-anonymized 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

  • nutritional supplementations
  • high myopia
  • optometry
  • cell therapy
  • drug delivery
  • age-related macular degeneration
  • glaucoma
  • retinal degeneration
  • choroidal thinning
  • scleral remodeling
  • light therapy
  • digital healthcare
  • prematurity of retionopathy
  • carotid artery occlusion
  • retinal ischemia
  • inflammation
  • eye drop

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Published Papers (6 papers)

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Editorial

Jump to: Research, Review

5 pages, 216 KB  
Editorial
Special Issue: Molecular Mechanisms and Treatment of Retinal Diseases
by Deokho Lee and Livio Vitiello
Int. J. Mol. Sci. 2026, 27(3), 1376; https://doi.org/10.3390/ijms27031376 - 30 Jan 2026
Viewed by 775
Abstract
The retina, one of the most metabolically active tissues in the human body, is susceptible to a wide range of injuries [...] Full article
(This article belongs to the Special Issue Molecular Mechanisms and Treatment of Retinal Diseases)

Research

Jump to: Editorial, Review

17 pages, 4240 KB  
Article
Topical Administration of Sitagliptin Prevents Retinal Neurodegeneration in a Model of Glaucoma Induced by Dexamethasone
by Patricia Bogdanov, Anna Duarri, David Sabater, María José Canz, Helena Isla-Magrané, Hugo Ramos, Anna Deàs-Just, Rafael Simó and Cristina Hernández
Int. J. Mol. Sci. 2026, 27(1), 48; https://doi.org/10.3390/ijms27010048 - 20 Dec 2025
Cited by 4 | Viewed by 1839
Abstract
Glaucoma is a neurodegenerative disease characterized by progressive degeneration of optic nerve axons and loss of retinal ganglion cells (RGCs). Although elevated intraocular pressure (IOP) is a major risk factor, many patients develop glaucoma with normal IOP, highlighting the need for neuroprotective therapies. [...] Read more.
Glaucoma is a neurodegenerative disease characterized by progressive degeneration of optic nerve axons and loss of retinal ganglion cells (RGCs). Although elevated intraocular pressure (IOP) is a major risk factor, many patients develop glaucoma with normal IOP, highlighting the need for neuroprotective therapies. Sitagliptin, a dipeptidyl peptidase-4 inhibitor, has shown beneficial effects in diabetes-induced retinal neurodegeneration. This study aimed to evaluate whether sitagliptin eye drops, previously effective in diabetes-induced retinal neurodegeneration, could prevent corticosteroid-induced glaucoma. Glaucoma was induced in mice by periocular injection of dexamethasone (DEX) once weekly for five weeks. Sitagliptin or vehicle eye drops were administered from day 14 to 35. Untreated mice served as controls. DEX treatment caused significant loss of RGC bodies and optic nerve axons compared to controls, which was prevented by sitagliptin eye drops (p < 0.001), without affecting IOP. Sitagliptin also inhibited DEX-induced activation of macroglia and microglia and prevented oligodendrocyte loss. Furthermore, it suppressed overexpression of galectin-3 and gamma-synuclein in the optic nerve head (ONH) (p < 0.001), key mediators of inflammation and apoptosis. Sitagliptin eye drops exert a potent neuroprotective effect against corticosteroid-induced glaucoma, supporting their potential as a novel therapeutic strategy for glaucoma. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Treatment of Retinal Diseases)
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19 pages, 899 KB  
Article
Evaluation of the Duration of Good Visual Acuity During Anti-VEGF Therapy for Age-Related Macular Degeneration in Routine Clinical Practice
by Andrea Gyenes, Lilla István, András Papp, Miklós Resch, Zsuzsa Récsán, Mónika Ecsedy, Zsuzsanna Szepessy, Antal Szabó, Balázs Lesch, György Barcsay, Ágnes Borbándy, Gábor László Sándor, Zoltán Z. Nagy and Illés Kovács
Int. J. Mol. Sci. 2025, 26(22), 10927; https://doi.org/10.3390/ijms262210927 - 11 Nov 2025
Cited by 1 | Viewed by 2044
Abstract
The aim of this study was to analyse data from a clinical database using a novel visual acuity parameter to determine whether anti-VEGF molecules that target multiple domains involved in neovascularisation are more likely to achieve good visual acuity than agents that solely [...] Read more.
The aim of this study was to analyse data from a clinical database using a novel visual acuity parameter to determine whether anti-VEGF molecules that target multiple domains involved in neovascularisation are more likely to achieve good visual acuity than agents that solely inhibit VEGF. This retrospective study analysed data from patients treated with anti-VEGF injections between 2015 and 2023. We set an ETDRS score threshold of 70 (equivalent to 20/40 Snellen acuity) to calculate ‘time in range’ (TIR). TIR is defined as ‘time spent with best-corrected visual acuity (BCVA) better than 20/40’ and can highlight significant variations in the time individuals spend above the threshold during their AMD treatment. Over nine years, 30,209 aflibercept and 10,876 ranibizumab injections were administered to 6043 patients. Patients received an average of 6.8 injections. The mean BCVA at the first injection was 57.00 ± 16.15 ETDRS letters for ranibizumab patients and 58.75 ± 15.82 for aflibercept patients, with a statistically significant difference (p < 0.001). Both groups showed significant improvement in visual acuity at follow-up (aflibercept: 60.21 ± 15.53; ranibizumab: 59.43 ± 15.81; both p < 0.001). The mean time between the two consecutive injections, including both the initial loading phase and the subsequent maintenance phase, was 67.22 ± 34.08 days for ranibizumab and 72.15 ± 31.00 days for aflibercept; the difference was statistically significant (p < 0.001). After controlling for the effect of initial BCVA and time between injections, patients who received aflibercept had a significantly higher average TIR (60.90 ± 36.27 days vs. 56.55 ± 38.78 days, p < 0.001), and significantly more likely to achieve >70 letters at the next visit (OR: 1.10; 95% CI: 1.05–1.15; p < 0.001) compared to patients receiving ranibizumab. Aflibercept treatment improves the likelihood of maintaining good BCVA by 10% compared to ranibizumab in patients receiving intravitreal anti-VEGF treatment for nAMD. Furthermore, the beneficial effects of aflibercept treatment are observed with less frequent dosing. Our results suggest that using anti-VEGF compounds that target multiple domains provides a detectable advantage in treating age-related macular degeneration, particularly when these agents have a longer duration of action. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Treatment of Retinal Diseases)
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34 pages, 9495 KB  
Article
Specific Assay Protocols for Porcine Single-Eye Retinal Pigment Epithelium Concerning Oxidative Stress and Inflammation
by Philipp Dörschmann, Marie Prinz, Greta Schmitkall, Johann Roider and Alexa Klettner
Int. J. Mol. Sci. 2025, 26(17), 8434; https://doi.org/10.3390/ijms26178434 - 29 Aug 2025
Cited by 3 | Viewed by 1523
Abstract
The retinal pigment epithelium (RPE) is strongly involved in the pathogenesis of several retinal diseases, such as age-related macular degeneration (AMD). RPE models addressing specific pathological pathways are of high importance for understanding cellular pathomechanisms and pre-clinical screening of potential new therapeutics. The [...] Read more.
The retinal pigment epithelium (RPE) is strongly involved in the pathogenesis of several retinal diseases, such as age-related macular degeneration (AMD). RPE models addressing specific pathological pathways are of high importance for understanding cellular pathomechanisms and pre-clinical screening of potential new therapeutics. The goal of this study is to establish standard operation protocols for single-eye porcine RPE preparation for AMD-relevant models of oxidative stress (RPE-Ox) and inflammation (RPE-Inf). Porcine primary RPE were prepared from one eye and seeded into one well of 12-well plates or, for polar differentiation, in transwell inserts. Different coatings (Poly-ᴅ-Lysine and laminin) and serum content of media (10%, 5%, and 1%) were tested to determine optimal culture parameters. For RPE-Ox, cells were treated with NaIO3, CoCl2, or erastin; cell viability (thiazolyl blue tetrazolium bromide, MTT), and gene expression (RT-qPCR) were determined. For RPE-Inf, cells were treated with lipopolysaccharide (LPS), polyinosinic/polycytidylic acid (Poly I:C), or tumor necrosis factor alpha (TNF-α); cell viability (MTT), cytokine secretion (ELISA), and gene expression (RT-qPCR) were determined. For transwell plates in RPE-Inf, cell viability (MTT), polar cytokine secretion (ELISA), gene expression (RT-qPCR), and transepithelial electrical resistance (TEER) for barrier assessment were conducted. For RPE-Ox, effective LD50 could be achieved by using 24 h stimulation with 25 µm erastin, seven days after preparation in 5% serum cultures, without coating. For gene expression assessment, the use of Poly-ᴅ-Lysine is recommended. For RPE-Inf, three days of LPS stimulation (1 µg/mL) showed effective cytokine activation with 5% serum on uncoated 12-well plates. Transwell plates are not recommended for cytokine secretion assessment. It can be used for cell barrier assays in which LPS also showed effective cell barrier decrease and gene expression assays. Two specific best practice protocols for the use of porcine single-eye cultures in AMD research concerning oxidative stress and inflammation with optimized parameters were established and are provided. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Treatment of Retinal Diseases)
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Review

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17 pages, 1821 KB  
Review
Sub-Internal Limiting Membrane Hemorrhage: Molecular Microenvironment and Review of Treatment Modalities
by Krzysztof Eder, Paulina Langosz, Marta Danikiewicz-Zagała, Rafał Leszczyński and Dorota Wyględowska-Promieńska
Int. J. Mol. Sci. 2026, 27(3), 1336; https://doi.org/10.3390/ijms27031336 - 29 Jan 2026
Cited by 2 | Viewed by 1562
Abstract
Sub-internal limiting membrane (sub-ILM) hemorrhage is a distinct preretinal bleeding entity in which blood accumulates between the ILM and the retinal nerve fiber layer (RNFL), forming a sharply confined compartment. The ILM’s low permeability and lack of immune cell access create a stagnant [...] Read more.
Sub-internal limiting membrane (sub-ILM) hemorrhage is a distinct preretinal bleeding entity in which blood accumulates between the ILM and the retinal nerve fiber layer (RNFL), forming a sharply confined compartment. The ILM’s low permeability and lack of immune cell access create a stagnant microenvironment in which erythrocyte lysis leads to the accumulation of hemoglobin, heme, and iron, promoting the generation of reactive oxygen species. This oxidative burden poses a direct risk to retinal ganglion cells and Müller cell endfeet. Spectral-domain optical coherence tomography (SD-OCT) enables precise identification of sub-ILM blood through its characteristic dome-shaped elevation and hyperreflective contents, distinguishing it from subhyaloid and vitreous hemorrhage. Management options include observation, neodymium-doped yttrium–aluminum–garnet (Nd: YAG) laser membranotomy, pneumatic displacement, and pars plana vitrectomy (PPV). While small, extrafoveal hemorrhages may resolve spontaneously, prolonged blood entrapment is associated with increased retinal toxicity, tractional changes, and proliferative vitreoretinopathy (PVR). Early intervention generally results in faster clearance and improved visual outcomes, particularly for dense or foveal bleeding. Major gaps remain regarding cellular stress responses, biomarkers that predict irreversible damage, and the optimal timing of intervention. Standardized imaging criteria and evidence-based management algorithms are needed to guide individualized treatment. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Treatment of Retinal Diseases)
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25 pages, 738 KB  
Review
Diabetic Retinopathy, a Comprehensive Overview on Pathophysiology and Relevant Experimental Models
by Kate Gettinger, Deokho Lee, Yohei Tomita, Kazuno Negishi and Toshihide Kurihara
Int. J. Mol. Sci. 2025, 26(20), 9882; https://doi.org/10.3390/ijms26209882 - 11 Oct 2025
Cited by 22 | Viewed by 13387
Abstract
Diabetic retinopathy (DR) is a serious complication of diabetes, leading to vision loss worldwide. The prevalence of DR has increased in recent decades. To understand the pathophysiology of DR, various experimental models have been developed and used. In this review article, we first [...] Read more.
Diabetic retinopathy (DR) is a serious complication of diabetes, leading to vision loss worldwide. The prevalence of DR has increased in recent decades. To understand the pathophysiology of DR, various experimental models have been developed and used. In this review article, we first outline what is currently known of the general pathology of DR, including the mechanisms involved in hyperglycemia, vascular dysfunction, retinal ischemia, retinal inflammation, and retinal degeneration. We next summarize various pathologies detected in experimental models in vivo, such as in chemically and genetically induced murine, rat, and monkey models, surgical methods in larger animals like cats, and a novel murine DR model using occlusion of the carotid artery under early diabetic conditions. A general overview of the in vitro models, including cell monocultures, co-cultures, and 3D models, is also provided. This current summary enables further research to obtain a more thorough understanding of DR pathogenesis and develop appropriate treatment measures. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Treatment of Retinal Diseases)
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