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New Molecular Insights and Therapeutic Strategies for Ocular Vascular Pathologies

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Dr. Raquel Lima e Silva

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Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Interests: choroidal neovascularization; eye; retina; retinal vessels; retinal neovascularization; vascular endothelial growth factor; drug delivery therapy

Special Issue Information

Dear Colleagues,

We invite you to contribute to our Special Issue entitled “New Molecular Insights and Therapeutic Strategies for Ocular Vascular Pathologies”.

This Special Issue aims to highlight innovative research and reviews on the pathogenesis and treatment of ocular vascular diseases, such as diabetic retinopathy, age-related macular degeneration, and retinal vein occlusion, which remain the leading causes of vision impairment and blindness globally. Progress in molecular biology and biotechnology has deepened our understanding of the underlying mechanisms of these conditions, paving the way for innovative therapeutic strategies.

We welcome papers that address molecular insights, including the VEGF pathway, the role of inflammation and cytokines, and the importance of oxidative stress in ocular pathologies. In addition, we are interested in papers investigating recent advances in therapeutic strategies for retinal and choroidal diseases, including new approaches for delivering anti-VEGF therapies, anti-inflammatory agents, gene therapy, antioxidants, neuroprotective agents, and stem cell therapy.

We look forward to your valuable contributions to this Special Issue, which aims to advance our understanding and treatment of ocular vascular pathologies.

This Special Issue is now open for submissions. If you are interested in contributing your work, please send a short abstract or tentative title to the Guest Editor or Editorial Office.

Dr. Raquel Lima e Silva
Guest Editor

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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.

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Published Papers (2 papers)

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Research

18 pages, 2600 KiB

Open AccessArticle

Nintedanib Induces Mesenchymal-to-Epithelial Transition and Reduces Subretinal Fibrosis Through Metabolic Reprogramming

by David Hughes, Jüergen Prestle, Nina Zippel, Sarah McFetridge, Manon Szczepan, Heike Neubauer, Heping Xu and Mei Chen

Int. J. Mol. Sci. 2025, 26(15), 7131; https://doi.org/10.3390/ijms26157131 - 24 Jul 2025

Viewed by 242

Abstract

This study aimed to investigate the tyrosine kinase inhibitor Nintedanib and its potential role in reversing epithelial–mesenchymal transition (EMT) induced by transforming growth factor beta 2 (TGF-β2) in retinal pigment epithelial (RPE) cells, along with its therapeutic potential using a mouse model of subretinal fibrosis. We hypothesized that the blockade of angiogenesis promoting and fibrosis inducing signaling using the receptor tyrosine kinase inhibitor Nintedanib (OfevTM) can prevent or reverse EMT both in vitro and in our in vivo model of subretinal fibrosis. Primary human retinal pigment epithelial cells (phRPE) and adult retinal pigment epithelial cell line (ARPE-19) cells were treated with TGF-β210 ng/mL for two days followed by four days of Nintedanib (1 µM) incubation. Epithelial and mesenchymal phenotypes were assessed by morphological examination, quantitative real-time polymerase chain reaction(qPCR) (ZO-1, Acta2, FN, and Vim), and immunocytochemistry (ZO-1, vimentin, fibronectin, and αSMA). Metabolites were measured using luciferase-based assays. Extracellular acidification and oxygen consumption rates were measured using the Seahorse XF system. Metabolic-related genes (GLUT1, HK2, PFKFB3, CS, LDHA, LDHB) were evaluated by qPCR. A model of subretinal fibrosis using the two-stage laser-induced method in C57BL/6J mice assessed Nintedanib’s therapeutic potential. Fibro-vascular lesions were examined 10 days later via fluorescence angiography and immunohistochemistry. Both primary and ARPE-19 RPE stimulated with TGF-β2 upregulated expression of fibronectin, αSMA, and vimentin, and downregulation of ZO-1, consistent with morphological changes (i.e., elongation). Glucose consumption, lactate production, and glycolytic reserve were significantly increased in TGF-β2-treated cells, with upregulation of glycolysis-related genes (GLUT1, HK2, PFKFB3, CS). Nintedanib treatment reversed TGF-β2-induced EMT signatures, down-regulated glycolytic-related genes, and normalized glycolysis. Nintedanib intravitreal injection significantly reduced collagen-1+ fibrotic lesion size and Isolectin B4+ neovascularization and reduced vascular leakage in the two-stage laser-induced model of subretinal fibrosis. Nintedanib can induce Mesenchymal-to-Epithelial Transition (MET) in RPE cells and reduce subretinal fibrosis through metabolic reprogramming. Nintedanib can therefore potentially be repurposed to treat retinal fibrosis. Full article

(This article belongs to the Special Issue New Molecular Insights and Therapeutic Strategies for Ocular Vascular Pathologies)

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11 pages, 1397 KiB

Open AccessArticle

Prolonged Photobiomodulation with Deep Red Light Mitigates Incipient Retinal Deterioration in a Mouse Model of Type 2 Diabetes

by Gabriela Opazo, Felipe Tapia, Alejandra Díaz, Alex H. Vielma and Oliver Schmachtenberg

Int. J. Mol. Sci. 2024, 25(22), 12128; https://doi.org/10.3390/ijms252212128 - 12 Nov 2024

Viewed by 1143

Abstract

Diabetic retinopathy is a prevalent complication of type 2 diabetes mellitus, characterized by progressive damage to the retinal structure and function. Photobiomodulation therapy, using red or near-infrared light, has been proposed as a non-invasive intervention to mitigate retinal damage, but has been tested generally with short-term stimuli. This study aimed to evaluate the effects of prolonged photobiomodulation with deep red light on retinal structure and function in a type 2 diabetes mouse model. Transgenic LepRdb/J (db/db) mice were exposed to photobiomodulation therapy via LED devices emitting 654 nm light for 12 h daily over ten weeks and compared to untreated mice. Retinal function was evaluated by flash electroretinography, while structural changes were assessed through histology and immunohistochemistry to detect astro- and microgliosis. At 33 weeks of age, db/db mice were obese and severely diabetic, but exhibited only incipient indicators of retinal deterioration. Electroretinogram b-wave peak latencies were prolonged at intermediate flash intensities, while the outer plexiform layer displayed significantly elevated IBA1 expression. Photobiomodulation therapy prevented these two markers of early retinal deterioration but had no effect on other morphological and functional parameters. Photobiomodulation is well-tolerated and maintains potential as a complementary treatment option for diabetic retinopathy but requires further optimization of therapeutic settings and combinatory treatment approaches. Full article

(This article belongs to the Special Issue New Molecular Insights and Therapeutic Strategies for Ocular Vascular Pathologies)

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