# The Central Role of Oxidative Stress in Diabetic Retinopathy: Advances in Pathogenesis, Diagnosis, and Therapy

**Authors:** Nicolas Tuli, Harry Moroz, Armaan Jaffer, Merve Kulbay, Stuti M. Tanya, Feyza Sule Aslan, Derman Ozdemir, Shigufa Kahn Ali, Cynthia X. Qian

PMC · DOI: 10.3390/diagnostics16030392 · Diagnostics · 2026-01-26

## TL;DR

This paper reviews how oxidative stress contributes to diabetic retinopathy and highlights new diagnostic and treatment approaches.

## Contribution

The paper provides a comprehensive review of recent advances in understanding DR pathogenesis and novel diagnostic and therapeutic strategies.

## Key findings

- Oxidative stress and VEGF-driven neovascularization are central to diabetic retinopathy pathology.
- AI-based algorithms and liquid biopsy are emerging as promising diagnostic tools for DR.
- Innovations like intravitreal implants are improving drug delivery for DR treatment.

## Abstract

Diabetic retinopathy (DR) remains the leading cause of preventable blindness among working-age adults worldwide, driven by the growing prevalence of diabetes mellitus. The aim of this comprehensive literature review is to provide an insightful analysis of recent advances in the pathogenesis of DR, followed by a summary of emerging technologies for its diagnosis and treatment. Recent studies have explored the roles of cell death pathways, immune activation, and lipid peroxidation in the pathology of DR. However, at the core of DR pathology lies neovascularization driven by vascular endothelial growth factor (VEGF), and mitochondrial damage due to dysregulated oxidative stress. These dysregulated pathways manifest clinically as DR, with specific subtypes including non-proliferative DR, proliferative DR and diabetic macular edema, which can be diagnosed through various imaging modalities. Recently, novel advances have been made using liquid biopsy and artificial (AI)-based algorithms with the goal of transforming DR diagnostics. AI models show distinct promise with the capacity to provide automated interpretation of retinal imaging. Furthermore, conventional anti-VEGF injectable agents have revolutionized DR treatment in the past decades. Today, as the pathogenesis of DR becomes better understood, new pathways, such as the ROS-VEGF loop, are being elucidated in greater depth, enabling the development of targeted therapies. In addition, new innovations such as intravitreal implants are transforming the delivery of DR-specific medication. This paper will discuss the current understanding of the pathogenesis of DR, which is leading to new diagnostic and therapeutic tools that will transform clinical management of DR.

## Linked entities

- **Proteins:** VEGFA (vascular endothelial growth factor A)
- **Diseases:** diabetic retinopathy (MONDO:0005266), diabetes mellitus (MONDO:0005015), diabetic macular edema (MONDO:0004728)

## Full-text entities

- **Genes:** VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}
- **Diseases:** diabetic macular edema (MESH:D008269), mitochondrial damage (MESH:D028361), blindness (MESH:D001766), DR (MESH:D003930), diabetes mellitus (MESH:D003920)
- **Chemicals:** lipid (MESH:D008055)

## Full text

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## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12896838/full.md

## References

339 references — full list in the complete paper: https://tomesphere.com/paper/PMC12896838/full.md

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Source: https://tomesphere.com/paper/PMC12896838