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Selective Activation of the Wnt-Signaling Pathway as a Novel Therapy for the Treatment of Diabetic Retinopathy and Other Retinal Vascular Diseases

Retinal ischemia, often associated with various disorders such as diabetic retinopathy (DR), retinal vein occlusion, glaucoma, optic neuropathies, stroke, and other retinopathies, is a major cause of visual impairment and blindness worldwide. As proper blood supply to the retina is critical to maint...

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Autores principales: Nguyen, Huy, Lee, Sung-Jin, Li, Yang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9697247/
https://www.ncbi.nlm.nih.gov/pubmed/36432666
http://dx.doi.org/10.3390/pharmaceutics14112476
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author Nguyen, Huy
Lee, Sung-Jin
Li, Yang
author_facet Nguyen, Huy
Lee, Sung-Jin
Li, Yang
author_sort Nguyen, Huy
collection PubMed
description Retinal ischemia, often associated with various disorders such as diabetic retinopathy (DR), retinal vein occlusion, glaucoma, optic neuropathies, stroke, and other retinopathies, is a major cause of visual impairment and blindness worldwide. As proper blood supply to the retina is critical to maintain its high metabolic demand, any impediment to blood flow can lead to a decrease in oxygen supply, resulting in retinal ischemia. In the pathogenesis of DR, including diabetic macular edema (DME), elevated blood glucose leads to blood-retina barrier (BRB) disruptions, vascular leakage, and capillary occlusion and dropouts, causing insufficient delivery of oxygen to the retina, and ultimately resulting in visual impairment. Other potential causes of DR include neuronal dysfunction in the absence of vascular defect, genetic, and environmental factors. The exact disease progression remains unclear and varies from patient to patient. Vascular leakage leading to edema clearly links to visual impairment and remains an important target for therapy. Despite recent advances in the treatment of DME and DR with anti-VEGFs, effective therapies with new mechanisms of action to address current treatment limitations regarding vessel regeneration and reperfusion of ischemic retinal areas are still needed. The Wnt signaling pathway plays a critical role in proper vascular development and maintenance in the retina, and thus provides a novel therapeutic approach for the treatment of diabetic and other retinopathies. In this review, we summarize the potential of this pathway to address treatment gaps with current therapies, its promise as a novel and potentially disease modifying therapy for patients with DR and opportunities in other retinal vascular diseases.
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spelling pubmed-96972472022-11-26 Selective Activation of the Wnt-Signaling Pathway as a Novel Therapy for the Treatment of Diabetic Retinopathy and Other Retinal Vascular Diseases Nguyen, Huy Lee, Sung-Jin Li, Yang Pharmaceutics Review Retinal ischemia, often associated with various disorders such as diabetic retinopathy (DR), retinal vein occlusion, glaucoma, optic neuropathies, stroke, and other retinopathies, is a major cause of visual impairment and blindness worldwide. As proper blood supply to the retina is critical to maintain its high metabolic demand, any impediment to blood flow can lead to a decrease in oxygen supply, resulting in retinal ischemia. In the pathogenesis of DR, including diabetic macular edema (DME), elevated blood glucose leads to blood-retina barrier (BRB) disruptions, vascular leakage, and capillary occlusion and dropouts, causing insufficient delivery of oxygen to the retina, and ultimately resulting in visual impairment. Other potential causes of DR include neuronal dysfunction in the absence of vascular defect, genetic, and environmental factors. The exact disease progression remains unclear and varies from patient to patient. Vascular leakage leading to edema clearly links to visual impairment and remains an important target for therapy. Despite recent advances in the treatment of DME and DR with anti-VEGFs, effective therapies with new mechanisms of action to address current treatment limitations regarding vessel regeneration and reperfusion of ischemic retinal areas are still needed. The Wnt signaling pathway plays a critical role in proper vascular development and maintenance in the retina, and thus provides a novel therapeutic approach for the treatment of diabetic and other retinopathies. In this review, we summarize the potential of this pathway to address treatment gaps with current therapies, its promise as a novel and potentially disease modifying therapy for patients with DR and opportunities in other retinal vascular diseases. MDPI 2022-11-16 /pmc/articles/PMC9697247/ /pubmed/36432666 http://dx.doi.org/10.3390/pharmaceutics14112476 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Nguyen, Huy
Lee, Sung-Jin
Li, Yang
Selective Activation of the Wnt-Signaling Pathway as a Novel Therapy for the Treatment of Diabetic Retinopathy and Other Retinal Vascular Diseases
title Selective Activation of the Wnt-Signaling Pathway as a Novel Therapy for the Treatment of Diabetic Retinopathy and Other Retinal Vascular Diseases
title_full Selective Activation of the Wnt-Signaling Pathway as a Novel Therapy for the Treatment of Diabetic Retinopathy and Other Retinal Vascular Diseases
title_fullStr Selective Activation of the Wnt-Signaling Pathway as a Novel Therapy for the Treatment of Diabetic Retinopathy and Other Retinal Vascular Diseases
title_full_unstemmed Selective Activation of the Wnt-Signaling Pathway as a Novel Therapy for the Treatment of Diabetic Retinopathy and Other Retinal Vascular Diseases
title_short Selective Activation of the Wnt-Signaling Pathway as a Novel Therapy for the Treatment of Diabetic Retinopathy and Other Retinal Vascular Diseases
title_sort selective activation of the wnt-signaling pathway as a novel therapy for the treatment of diabetic retinopathy and other retinal vascular diseases
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9697247/
https://www.ncbi.nlm.nih.gov/pubmed/36432666
http://dx.doi.org/10.3390/pharmaceutics14112476
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