Protecting Neurons in Retinal and Optic Nerve Diseases: The Role of Ferroptosis-Associated Pathways
- 1Department of Ophthalmology, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
Abstract
Retinal ischemia (RI) is a prominent pathological feature of several ocular diseases, including diabetic retinopathy, glaucoma, and retinopathy of prematurity. These diseases are major causes of adult and childhood blindness worldwide. Retinal and optic nerve degeneration also involves non-ischemic mechanisms. Severe or sustained RI can cause irreversible retinal injury and visual impairment. RI can trigger oxidative stress, inflammatory responses, and mitochondrial dysfunction, which can contribute to cell death. Ferroptosis is a distinct form of regulated cell death characterized by the iron-dependent accumulation of lethal lipid peroxides in membrane phospholipids. Accumulating preclinical evidence indicates that ferroptosis-associated processes may contribute to retinal and optic nerve injury. Targeting ferroptosis-related pathways may offer promising approaches to mitigate cellular damage in these diseases. In this review, we summarize the ferroptosis mechanisms relevant to retinal and optic nerve injury and evaluate evidence from experimental models, cell types, pharmacological rescue studies, and genetic approaches. By comparing experimental models, cell types, and mechanistic evidence, we distinguish direct neuronal findings from non-neuronal ocular responses and assess whether the results support ferroptosis or broader oxidative stress. We also identify the evidence needed to assess the translational relevance of ferroptosis-targeted strategies in retinal and optic nerve diseases.
Related
- Commentary: Wogonoside alleviates metabolic dysfunction-associated steatohepatitis by modulating AMPK and xCT/GPX4 pathways to restrain lipid dysregulation and ferroptosis
- Targeting Caveolin-1 Alleviated Diabetic Retinopathy Injury through Protecting Müller Cells from Ferroptosis via the xCT/GPX4 Signaling Pathway
- Protecting public health in mining: a Q-methodology examination of policy space and reform pathways in Tanzania.
- Parkinson's disease LRRK2 mutations dysregulate iron homeostasis and promote oxidative stress and ferroptosis in human neurons and astrocytes.
- Long-chain acyl-CoA synthetases in female reproductive diseases: isoform-specific regulation of lipid metabolism, ferroptosis, and inflammatory signaling
BibTeX
@article{xiang2026protecting,
title = {{Protecting Neurons in Retinal and Optic Nerve Diseases: The Role of Ferroptosis-Associated Pathways}},
author = {Lu Xiang and Xiaoyuan Ye and Amy Cheuk Yin Lo},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27219601},
url = {https://www.mdpi.com/1422-0067/27/21/9601},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Protecting Neurons in Retinal and Optic Nerve Diseases: The Role of Ferroptosis-Associated Pathways
AU - Lu Xiang
AU - Xiaoyuan Ye
AU - Amy Cheuk Yin Lo
PY - 2026
DA - 2026/10/27
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219601
UR - https://www.mdpi.com/1422-0067/27/21/9601
AB - Retinal ischemia (RI) is a prominent pathological feature of several ocular diseases, including diabetic retinopathy, glaucoma, and retinopathy of prematurity. These diseases are major causes of adult and childhood blindness worldwide. Retinal and optic nerve degeneration also involves non-ischemic mechanisms. Severe or sustained RI can cause irreversible retinal injury and visual impairment. RI can trigger oxidative stress, inflammatory responses, and mitochondrial dysfunction, which can contribute to cell death. Ferroptosis is a distinct form of regulated cell death characterized by the iron-dependent accumulation of lethal lipid peroxides in membrane phospholipids. Accumulating preclinical evidence indicates that ferroptosis-associated processes may contribute to retinal and optic nerve injury. Targeting ferroptosis-related pathways may offer promising approaches to mitigate cellular damage in these diseases. In this review, we summarize the ferroptosis mechanisms relevant to retinal and optic nerve injury and evaluate evidence from experimental models, cell types, pharmacological rescue studies, and genetic approaches. By comparing experimental models, cell types, and mechanistic evidence, we distinguish direct neuronal findings from non-neuronal ocular responses and assess whether the results support ferroptosis or broader oxidative stress. We also identify the evidence needed to assess the translational relevance of ferroptosis-targeted strategies in retinal and optic nerve diseases.
SN - 1422-0067
ER -