Targeting Retinal Neuroglial Vascular Unit Damage - Novel Therapeutic Strategies for Early-Stage Diabetic Retinopathy

Sep 29, 2026

Diabetic retinopathy is a common chronic ocular microvascular complication of diabetes and a leading cause of vision loss. Neuroglial vascular unit injury occurs early and drives distinct retinal changes, linking impaired visual function to upstream NGVU dysfunction rather than later microvascular degeneration. This review synthesizes preclinical evidence identifying molecular targets that mitigate NGVU impairment, emphasizing translational value for preventing and treating early-stage disease before irreversible visual damage limits efficacy.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages8

Reading Time20 min

AccessFree to download

1. Introduction

2. Pathogenesis of NGVU Associated With DR Lesions

2.1. Composition of the NGVU

2.2. NGVU-Related Pathogenesis

Wiley Journal of Diabetes Research Volume 2025, Article ID 6922946, 8 pages [https://doi.org/10.1155/jdr/6922946](https://doi.org/10.1155/jdr/6922946) Review Article Targeting Retinal Neuroglial Vascular Unit Damage: Novel Therapeutic Strategies for Early-Stage Diabetic Retinopathy Xiaodong Li 1 and Hui Zhou 2 1Department of Ophthalmology, The First Aﬃliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, China 2Department of Ophthalmology, Hospital of Jianyang Traditional Chinese Medicine, Jianyang, China Correspondence should be addressed to Hui Zhou; [1573257277@qq.com](1573257277@qq.com) Received 12 April 2025; Revised 14 October 2025; Accepted 5 November 2025 Academic Editor: Eleonore Fröhlich Copyright © 2025 Xiaodong Li and Hui Zhou. Journal of Diabetes Research published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. Diabetic retinopathy (DR) is a prevalent chronic ocular complication of diabetes, which ranks as the leading cause of blindness in individuals aged 40 and above. Recent studies have demonstrated that neuroglial vascular unit (NGVU) injury leads to distinct fundus changes in DR, including exudates, cotton-ﬂuﬀ spots, microangiomas, hemorrhages, and neovascularization. Currently, the primary clinical treatment options primarily target retinal microvascular degeneration during the middle and late stages of DR through techniques such as retinal laser photocoagulation, antivascular endothelial growth factor (VEGF) therapy, and vitrectomy. However, progression to these stages often results in irreversible damage to visual acuity with limited treatment eﬃcacy. In recent years, relevant research has conﬁrmed that NGVU injury occurs prior to retinal microangiopathy in patients with DR, and it is closely associated with impaired visual function. Therefore, targeting NGVU holds potential for future therapeutic interventions aimed at preventing and treating early-stage DR. This review identiﬁes six key molecular targets (P2X7 receptor, NLRP3 inﬂammasome, retinal microglial cell necroptosis pathway, spermine oxidase, and AQP4-AS1 lncRNA) that mitigate NGVU dysfunction in preclinical models. Literature search was conducted in PubMed/Embase using keywords“diabetic retinopathy,” “neuroglial vascular unit,” and “targeted therapy” (2018–2024), focusing on preclinical studies within vivo eﬃcacy data. Keywords: diabetic retinopathy; inﬂammatory pathways; neuroglial vascular unit (NGVU); retinal neurodegeneration; targeted therapy 1. Introduction The prevalence of DR, a common ocular chronic microvascular complication of diabetes mellitus, is approximately 30%–40% among diabetic patients globally [1] . With rapid socioeconomic development, changes in dietary structure, and the aging global population, the global prevalence of DR is expected to continue increasing in the future [2] . It is projected that by 2045, the number of DR patients in China will reach approximately 174.4 million [3] . Prolonged diabetic disease can lead to retinal neurodegeneration and microvascular damage associated with DR, resulting in chronic vision loss, severe visual dysfunction, and even blindness. Current treatments such as retinal laser photoco- agulation, vitreous injection of anti-VEGF agents, and vitrectomy have limited eﬃcacy. As the disease progresses to an advanced stage, visual impairment often becomes irreversible. Long-term anti-VEGF treatment and repeated surgeries signiﬁcantly increase the economic burden on both patients and society. Given the limited eﬃcacy of current mainstream regimens for treating retinal neurodegeneration, microvascular damage, and disease progression associated with DR, it is crucial to explore therapeutic targets for preventing and treating early stages of DR progression. Curre

FAQs

What is the role of the neuroglial vascular unit (NGVU) in diabetic retinopathy?

NGVU injury is described as an early primary pathological change in diabetic retinopathy. It involves neurons, glial cells, and microvascular components that collectively maintain retinal homeostasis and the blood–retinal barrier integrity.

Why do current diabetic retinopathy treatments have limited efficacy in advanced disease?

The document explains that standard therapies mainly target retinal microvascular degeneration in middle and late stages. Progression to these stages can cause irreversible visual acuity damage and reduce treatment efficacy.

Which therapeutic targets are highlighted for early-stage diabetic retinopathy based on NGVU dysfunction?

The review identifies six key molecular targets, including the P2X7 receptor, NLRP3 inflammasome, a retinal microglial necroptosis pathway, spermine oxidase, and the AQP4-AS1 lncRNA.

Sep 29, 2026

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