Work

Ferroptosis-Mediated Cell-Specific Damage: Molecular Cascades and Therapeutic Breakthroughs in Diabetic Retinopathy

Year: 2025

Type: article

Abstract: Diabetic retinopathy (DR), a leading cause of vision loss in diabetic patients, involves complex pathological mechanisms including neurodegeneration, microvascular damage, inflammation, and oxidative stress. Recent studies have identified ferroptosis-a ferrodependent cell death mechanism-as playing a pivotal role in DR development. Existing evidence indicates that oxidative stress and mitochondrial dysfunction induced by hyperglycemia may contribute to retinal damage through the ferroptosis pathway in DR. Ferroptosis inhibitors such as Ferostatin-1 have demonstrated protective effects against DR in animal models. The core mechanisms of ferroptosis involve iron homeostasis imbalance and lipid peroxidation, with key regulatory pathways including GPX4-dependent and non-dependent mechanisms (such as FSP1-CoQ10). Within the signaling network, Nrf2 inhibits ferroptosis, p53 promotes it, while Hippo/YAP functions are environment-dependent. Non-coding RNAs and epigenetic modifications (e.g., DNA methylation and histone modifications) also participate in regulation. In DR, iron overload, GPX4 dysfunction, and p53 upregulation collectively induce ferroptosis in various types of retinal cells, making these pathways potential therapeutic targets. This review not only elaborates the role of iron metabolism imbalance and ferroptosis pathway in the occurrence and development of DR but also summarizes the new therapeutic approaches of DR targeting ferroptosis pathway. Investigating the relationship between ferroptosis and DR not only helps unravel its core pathophysiological mechanisms but also provides theoretical foundations for developing novel therapeutic approaches.

Source: Antioxidants

DOI: 10.3390/antiox15010001

Authors: Yan Chen, Rongyu Wang, Nannan Zhang, Liangzhi Xu

Institutions: Sichuan University, West China Second University Hospital of Sichuan University

Language: English

Topic: Ferroptosis and cancer prognosis

Subfield: Pulmonary and Respiratory Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,499