Targeting oxidative stress in diabetic retinopathy: mechanisms, pathology, and novel treatment approaches

Diabetic retinopathy (DR) is a common and severe microvascular complication of diabetes, leading to vision impairment and blindness, particularly in working-age adults. Oxidative stress plays a central role in the pathogenesis of DR, with excessive reactive oxygen species (ROS) damaging retinal tiss...

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Main Authors: Wei He, Panli Tang, Hongbin Lv
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-06-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1571576/full
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author Wei He
Panli Tang
Hongbin Lv
author_facet Wei He
Panli Tang
Hongbin Lv
author_sort Wei He
collection DOAJ
description Diabetic retinopathy (DR) is a common and severe microvascular complication of diabetes, leading to vision impairment and blindness, particularly in working-age adults. Oxidative stress plays a central role in the pathogenesis of DR, with excessive reactive oxygen species (ROS) damaging retinal tissues, including blood vessels and neurons. This oxidative damage is exacerbated through various metabolic pathways, such as the polyol pathway, protein kinase C(PKC) activation, and advanced glycation end-product(AGE) formation. Additionally, mitochondrial dysfunction, retinal cell apoptosis, inflammation, and lipid peroxidation are key pathological processes associated with oxidative stress in DR. Epigenetic modifications, including DNA methylation and histone alterations, further contribute to gene expression changes induced by oxidative stress. To mitigate oxidative damage, therapeutic strategies targeting ROS production, neutralizing free radicals, and enhancing antioxidant defenses hold promise. Various natural antioxidant compounds, such as polyphenols (e.g., epigallocatechin-3-gallate, quercetin, resveratrol) and carotenoids (e.g., lutein, zeaxanthin), have demonstrated potential in reducing oxidative stress and improving retinal health in DR models. Moreover, activation of the Nrf2 and SIRT1 pathways has emerged as a promising approach to enhance the antioxidant response. Although preclinical studies show promising results, further clinical trials are necessary to validate the efficacy and safety of these therapeutic strategies. In conclusion, a better understanding of the molecular mechanisms underlying oxidative stress in DR and the development of multi-target therapies could provide more effective treatment options for DR patients.
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spelling doaj-art-37a3e3f0ecb041788b74bc0b68d0be902025-08-20T02:06:46ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-06-011610.3389/fimmu.2025.15715761571576Targeting oxidative stress in diabetic retinopathy: mechanisms, pathology, and novel treatment approachesWei He0Panli Tang1Hongbin Lv2Department of Ophthalmology, Taikang Sichuan Hospital, Chengdu, ChinaDepartment of Cardiothoracic Surgery, The General Hospital of Western Theater Command, Chengdu, ChinaDepartment of Ophthalmology, Affiliated Hospital of Southwest Medical University, Luzhou, ChinaDiabetic retinopathy (DR) is a common and severe microvascular complication of diabetes, leading to vision impairment and blindness, particularly in working-age adults. Oxidative stress plays a central role in the pathogenesis of DR, with excessive reactive oxygen species (ROS) damaging retinal tissues, including blood vessels and neurons. This oxidative damage is exacerbated through various metabolic pathways, such as the polyol pathway, protein kinase C(PKC) activation, and advanced glycation end-product(AGE) formation. Additionally, mitochondrial dysfunction, retinal cell apoptosis, inflammation, and lipid peroxidation are key pathological processes associated with oxidative stress in DR. Epigenetic modifications, including DNA methylation and histone alterations, further contribute to gene expression changes induced by oxidative stress. To mitigate oxidative damage, therapeutic strategies targeting ROS production, neutralizing free radicals, and enhancing antioxidant defenses hold promise. Various natural antioxidant compounds, such as polyphenols (e.g., epigallocatechin-3-gallate, quercetin, resveratrol) and carotenoids (e.g., lutein, zeaxanthin), have demonstrated potential in reducing oxidative stress and improving retinal health in DR models. Moreover, activation of the Nrf2 and SIRT1 pathways has emerged as a promising approach to enhance the antioxidant response. Although preclinical studies show promising results, further clinical trials are necessary to validate the efficacy and safety of these therapeutic strategies. In conclusion, a better understanding of the molecular mechanisms underlying oxidative stress in DR and the development of multi-target therapies could provide more effective treatment options for DR patients.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1571576/fulldiabetic retinopathyoxidative stressreactive oxygen speciesmitochondrial dysfunctiontherapeutic strategies
spellingShingle Wei He
Panli Tang
Hongbin Lv
Targeting oxidative stress in diabetic retinopathy: mechanisms, pathology, and novel treatment approaches
Frontiers in Immunology
diabetic retinopathy
oxidative stress
reactive oxygen species
mitochondrial dysfunction
therapeutic strategies
title Targeting oxidative stress in diabetic retinopathy: mechanisms, pathology, and novel treatment approaches
title_full Targeting oxidative stress in diabetic retinopathy: mechanisms, pathology, and novel treatment approaches
title_fullStr Targeting oxidative stress in diabetic retinopathy: mechanisms, pathology, and novel treatment approaches
title_full_unstemmed Targeting oxidative stress in diabetic retinopathy: mechanisms, pathology, and novel treatment approaches
title_short Targeting oxidative stress in diabetic retinopathy: mechanisms, pathology, and novel treatment approaches
title_sort targeting oxidative stress in diabetic retinopathy mechanisms pathology and novel treatment approaches
topic diabetic retinopathy
oxidative stress
reactive oxygen species
mitochondrial dysfunction
therapeutic strategies
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1571576/full
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AT panlitang targetingoxidativestressindiabeticretinopathymechanismspathologyandnoveltreatmentapproaches
AT hongbinlv targetingoxidativestressindiabeticretinopathymechanismspathologyandnoveltreatmentapproaches