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Advances in the Pathophysiology and Treatment of Diabetic Retinopathy

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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: 20 August 2025 | Viewed by 3313

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Special Issue Editors

Dr. Federico Gonzalez-Fernandez

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Guest Editor

1. Departments of Ophthalmology and Pathology, University of Mississippi Medical Center, Jackson, MS 39216, USA
2. Research & Development Service, G.V. (Sonny) Montgomery Veterans Affair Medical Center, Jackson, MS 39216, USA
Interests: fundamental retinal processes; ocular genetics; inflammation and immunology; retinal diseases; retinal neuroscience

Prof. Dr. Andrew Tsin

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Guest Editor

Department of Biomedical Sciences, University of Texas Rio Grande Valley School of Medicine, Edinburg, TX 78541, USA
Interests: biochemistry and molecular biology of visual cycle proteins; vascular endothelial growth factor; diabetic retinopathy and age-related macular degenerations

Special Issue Information

Dear Colleagues,

This Special Issue will include invited and refereed publications on recent advances in both basic and clinical research on diabetic retinopathy. An emphasis will be placed on early developmental events, including cellular and molecular mechanisms underlying diabetic retinopathy. In addition, this issue will highlight modern clinical intervention approaches in the prevention and treatment of diabetic retinopathy, with a strong emphasis on molecular biology and molecular medicine. Manuscripts purely based on clinical studies will not be considered.

Submission of manuscripts including original scientific research articles, comprehensive reviews, communications, case reports, letters and commentaries are welcome.

Dr. Federico Gonzalez-Fernandez
Prof. Dr. Andrew Tsin
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

diabetic retinopathy
age-related macular degenerations
retinal
vascular endothelial growth factor
visual system

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Published Papers (3 papers)

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Research

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19 pages, 1386 KiB

Open AccessArticle

Anterior Chamber Flare as a Non-Invasive Assessment of Intraocular Immune Status and Ocular Complications in Proliferative Diabetic Retinopathy

by Tomohito Sato, Yuki Takenaka, Yoshiaki Nishio, Masataka Ito and Masaru Takeuchi

Int. J. Mol. Sci. 2024, 25(17), 9158; https://doi.org/10.3390/ijms25179158 - 23 Aug 2024

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Abstract

Proliferative diabetic retinopathy (PDR) is a vision-threatening complication of diabetes mellitus (DM). Anterior chamber (AC) flare and intraocular cytokines are potent biomarkers reflecting the intraocular immune status in PDR. This study aimed to elucidate the complex interrelationship between AC flare and intraocular cytokines in PDR eyes. A retrospective observational study was conducted on 19 PDR eyes of 19 patients with type 2 DM, and on 19 eyes of 19 patients with idiopathic macular hole or epiretinal membrane as controls. AC flare was measured before pars plana vitrectomy (PPV). Aqueous humor (AH) and vitreous fluid (VF) samples were collected at the time of PPV, and the quantities of 27 cytokines in both intraocular fluids were analyzed. In the PDR and control groups, Spearman’s rank correlation analysis revealed a positive correlation between AC flare and IL-8 level in both AH and VF. Additionally, IL-8 levels in AH correlated positively with IL-8 levels in VF. In the PDR group, receiver operating characteristic curve analysis identified IL-8 level in AH as a significant predictor for both diabetic macular edema (DME) and vitreous hemorrhage (VH) complications. The cut-off values of IL-8 were established at ≥26.6 pg/mL for DME and ≥7.96 pg/mL for VH. Given the positive correlation between AC flare and AH IL-8 level, the present findings suggest that AC flare value may potentially be a non-invasive biomarker for predicting DME. Full article

(This article belongs to the Special Issue Advances in the Pathophysiology and Treatment of Diabetic Retinopathy)

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19 pages, 5473 KiB

Open AccessArticle

Arylphthalide Delays Diabetic Retinopathy via Immunomodulating the Early Inflammatory Response in an Animal Model of Type 1 Diabetes Mellitus

by Francisco Martín-Loro, Fátima Cano-Cano, María J. Ortega, Belén Cuevas, Laura Gómez-Jaramillo, María del Carmen González-Montelongo, Jan Cedric Freisenhausen, Almudena Lara-Barea, Antonio Campos-Caro, Eva Zubía, Manuel Aguilar-Diosdado and Ana I. Arroba

Int. J. Mol. Sci. 2024, 25(15), 8440; https://doi.org/10.3390/ijms25158440 - 2 Aug 2024

Cited by 1 | Viewed by 1640

Abstract

Diabetic retinopathy (DR) is one of the most prevalent secondary complications associated with diabetes. Specifically, Type 1 Diabetes Mellitus (T1D) has an immune component that may determine the evolution of DR by compromising the immune response of the retina, which is mediated by microglia. In the early stages of DR, the permeabilization of the blood–retinal barrier allows immune cells from the peripheral system to interact with the retinal immune system. The use of new bioactive molecules, such as 3-(2,4-dihydroxyphenyl)phthalide (M9), with powerful anti-inflammatory activity, might represent an advance in the treatment of diseases like DR by targeting the immune systems responsible for its onset and progression. Our research aimed to investigate the molecular mechanisms involved in the interaction of specific cells of the innate immune system during the progression of DR and the reduction in inflammatory processes contributing to the pathology. In vitro studies were conducted exposing Bv.2 microglial and Raw264.7 macrophage cells to proinflammatory stimuli for 24 h, in the presence or absence of M9. Ex vivo and in vivo approaches were performed in BB rats, an animal model for T1D. Retinal explants from BB rats were cultured with M9. Retinas from BB rats treated for 15 days with M9 via intraperitoneal injection were analyzed to determine survival, cellular signaling, and inflammatory markers using qPCR, Western blot, or immunofluorescence approaches. Retinal structure images were acquired via Spectral-Domain–Optical Coherence Tomography (SD-OCT). Our results show that the treatment with M9 significantly reduces inflammatory processes in in vitro, ex vivo, and in vivo models of DR. M9 works by inhibiting the proinflammatory responses during DR progression mainly affecting immune cell responses. It also induces an anti-inflammatory response, primarily mediated by microglial cells, leading to the synthesis of Arginase-1 and Hemeoxygenase-1(HO-1). Ultimately, in vivo administration of M9 preserves the retinal integrity from the degeneration associated with DR progression. Our findings demonstrate a specific interaction between both retinal and systemic immune cells in the progression of DR, with a differential response to treatment, mainly driven by microglia in the anti-inflammatory action. In vivo treatment with M9 induces a switch in immune cell phenotypes and functions that contributes to delaying the DR progression, positioning microglial cells as a new and specific therapeutic target in DR. Full article

(This article belongs to the Special Issue Advances in the Pathophysiology and Treatment of Diabetic Retinopathy)

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Review

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14 pages, 802 KiB

Open AccessReview

VEGF in Diabetic Retinopathy and Age-Related Macular Degeneration

by Andrew Callan, Justin Heckman, Giani Tah, Samantha Lopez, Laura Valdez and Andrew Tsin

Int. J. Mol. Sci. 2025, 26(11), 4992; https://doi.org/10.3390/ijms26114992 - 22 May 2025

Abstract

Vascular endothelial growth factor (VEGF) plays a key role in angiogenesis throughout the human body, influencing countless physiological and pathological processes, including tumor growth, preeclampsia, and retinal diseases such as diabetic retinopathy (DR) and age-related macular degeneration (AMD). In DR, VEGF promotes retinal neovascularization and intraretinal fluid accumulation, leading to complications like diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR). Regular intravitreal anti-VEGF injections are commonly used to manage PDR and DME, though repeated treatments are often required, and efficacy can be limited. AMD, a major cause of vision loss in older adults, is characterized by either dry or wet forms. While the dry form has not been shown to be influenced by VEGF, the choroidal neovascularization of wet AMD has strong associations with VEGF. Current treatment for wet AMD consists primarily of anti-VEGF injections, the gold standard of care, but is limited by varying patient responses, as treatments are often repeated every 4-8 weeks indefinitely. This review explores the pathogenic role of VEGF in both DR and AMD, discussing the molecular mechanisms underlying these diseases and the therapeutic approaches targeting VEGF. Despite advancements, the variability in treatment responses highlights the need for continued research to develop more effective therapies to prevent vision loss and blindness associated with these retinal diseases. Full article

(This article belongs to the Special Issue Advances in the Pathophysiology and Treatment of Diabetic Retinopathy)

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